diff --git a/CHANGES.txt b/CHANGES.txt
index 6734f757a6..2a28a86ceb 100644
--- a/CHANGES.txt
+++ b/CHANGES.txt
@@ -1,4 +1,5 @@
 2.1.12
+ * Fix potential NPE from handling result of SIM.highestSelectivityIndex (CASSANDRA-10550)
  * Fix paging issues with partitions containing only static columns data
    (CASSANDRA-10381)
  * Fix conditions on static columns (CASSANDRA-10264)
diff --git a/src/java/org/apache/cassandra/db/index/SecondaryIndexManager.java b/src/java/org/apache/cassandra/db/index/SecondaryIndexManager.java
index ad3aae8ab5..12a0a555b2 100644
--- a/src/java/org/apache/cassandra/db/index/SecondaryIndexManager.java
+++ b/src/java/org/apache/cassandra/db/index/SecondaryIndexManager.java
@@ -858,11 +858,14 @@ public class SecondaryIndexManager
         for (SecondaryIndexSearcher searcher : indexSearchers)
         {
             SecondaryIndex highestSelectivityIndex = searcher.highestSelectivityIndex(clause);
-            long estimate = highestSelectivityIndex.estimateResultRows();
-            if (estimate <= bestEstimate)
+            if (highestSelectivityIndex != null)
             {
-                bestEstimate = estimate;
-                mostSelective = searcher;
+                long estimate = highestSelectivityIndex.estimateResultRows();
+                if (estimate <= bestEstimate)
+                {
+                    bestEstimate = estimate;
+                    mostSelective = searcher;
+                }
             }
         }
 
diff --git a/src/java/org/apache/cassandra/service/StorageProxy.java b/src/java/org/apache/cassandra/service/StorageProxy.java
index f8b4f1c57f..4f20ef0273 100644
--- a/src/java/org/apache/cassandra/service/StorageProxy.java
+++ b/src/java/org/apache/cassandra/service/StorageProxy.java
@@ -1571,7 +1571,7 @@ public class StorageProxy implements StorageProxyMBean
                 {
                     // use our own mean column count as our estimate for how many matching rows each node will have
                     SecondaryIndex highestSelectivityIndex = searcher.highestSelectivityIndex(command.rowFilter);
-                    resultRowsPerRange = Math.min(resultRowsPerRange, highestSelectivityIndex.estimateResultRows());
+                    resultRowsPerRange = highestSelectivityIndex == null ? resultRowsPerRange : Math.min(resultRowsPerRange, highestSelectivityIndex.estimateResultRows());
                 }
             }
         }