diff --git a/cachecontrol/controller.py b/cachecontrol/controller.py
index 5eca8de7..8d80e67f 100644
--- a/cachecontrol/controller.py
+++ b/cachecontrol/controller.py
@@ -382,7 +382,8 @@ def cache_response(
         cache_url = self.cache_url(request.url)
         logger.debug('Updating cache with response from "%s"', cache_url)
 
-        # Delete it from the cache if we happen to have it stored there
+        # Don't cache a no-store response. Drop a stored entry only when it
+        # is the same variant; a different Vary variant stays.
         no_store = False
         if "no-store" in cc:
             no_store = True
@@ -390,10 +391,19 @@ def cache_response(
         if "no-store" in cc_req:
             no_store = True
             logger.debug('Request header has "no-store"')
-        if no_store and self.cache.get(cache_url):
-            logger.debug('Purging existing cache entry to honor "no-store"')
-            self.cache.delete(cache_url)
         if no_store:
+            # no-store applies to this response. A different Vary variant
+            # stored under the same URL is not this response.
+            cached_data = self.cache.get(cache_url)
+            if cached_data is not None:
+                same_variant = self.serializer.stored_variant_matches(
+                    request, cached_data
+                )
+                if same_variant is False:
+                    logger.debug("Keeping cached response for a different Vary variant")
+                else:
+                    logger.debug('Purging existing cache entry to honor "no-store"')
+                    self.cache.delete(cache_url)
             return
 
         # https://tools.ietf.org/html/rfc7234#section-4.1:
diff --git a/cachecontrol/serialize.py b/cachecontrol/serialize.py
index 83bce073..7ecb2057 100644
--- a/cachecontrol/serialize.py
+++ b/cachecontrol/serialize.py
@@ -132,6 +132,35 @@ def prepare_response(
 
         return HTTPResponse(body=body, preload_content=False, **cached["response"])
 
+    def stored_variant_matches(
+        self, request: PreparedRequest, data: object
+    ) -> bool | None:
+        """Return whether ``request`` selects the stored response.
+
+        False means the entry is a different Vary variant. None means the
+        entry is not a current cache record. This uses the same Vary check
+        as ``prepare_response``.
+        """
+        if not isinstance(data, bytes):
+            return None
+        prefix = f"cc={self.serde_version},".encode()
+        if not data.startswith(prefix):
+            return None
+        try:
+            cached = msgpack.loads(data[len(prefix) :], raw=False)
+        except (ValueError, TypeError):
+            return None
+        if not isinstance(cached, dict):
+            return None
+        vary = cached.get("vary", {})
+        if not isinstance(vary, dict) or "*" in vary:
+            return None
+
+        for header, value in vary.items():
+            if request.headers.get(header, None) != value:
+                return False
+        return True
+
     def _loads_v4(
         self,
         request: PreparedRequest,
diff --git a/tests/test_cache_control.py b/tests/test_cache_control.py
index 6e3f21bd..05eadf3c 100644
--- a/tests/test_cache_control.py
+++ b/tests/test_cache_control.py
@@ -113,6 +113,57 @@ def test_cache_response_no_store(self):
         cc.cache_response(self.req(), resp)
         assert not cc.cache.get(cache_url)
 
+    def test_no_store_keeps_different_vary_variant(self):
+        cache = DictCache()
+        cc = CacheController(cache)
+        now = time.strftime(TIME_FMT, time.gmtime())
+        json_req = DummyRequest(self.url, {"Accept": "application/json"})
+        json_resp = DummyResponse(
+            200,
+            {
+                "cache-control": "max-age=3600",
+                "date": now,
+                "vary": "Accept",
+            },
+        )
+        cc.cache_response(json_req, json_resp, b"json")
+        cached = cc.cache.get(self.url)
+        assert cached
+
+        html_req = DummyRequest(self.url, {"Accept": "text/html"})
+        html_resp = DummyResponse(
+            200,
+            {"cache-control": "no-store", "vary": "Accept"},
+        )
+        cc.cache_response(html_req, html_resp, b"html")
+
+        assert cc.cache.get(self.url) == cached
+        assert cc.serializer.loads(json_req, cached) is not None
+        assert cc.serializer.loads(html_req, cached) is None
+
+    def test_no_store_purges_same_vary_variant(self):
+        cache = DictCache()
+        cc = CacheController(cache)
+        now = time.strftime(TIME_FMT, time.gmtime())
+        req = DummyRequest(self.url, {"Accept": "application/json"})
+        resp = DummyResponse(
+            200,
+            {
+                "cache-control": "max-age=3600",
+                "date": now,
+                "vary": "Accept",
+            },
+        )
+        cc.cache_response(req, resp, b"json")
+        assert cc.cache.get(self.url)
+
+        cc.cache_response(
+            req,
+            DummyResponse(200, {"cache-control": "no-store", "vary": "Accept"}),
+            b"html",
+        )
+        assert cc.cache.get(self.url) is None
+
     def test_cache_control_directives_case_insensitive(self, cc):
         now = time.strftime(TIME_FMT, time.gmtime())
         resp = self.resp({"cache-control": "No-Store, max-age=3600", "date": now})