diff --git a/CHANGES.txt b/CHANGES.txt
index 4f5e8a72cc..560472ab74 100644
--- a/CHANGES.txt
+++ b/CHANGES.txt
@@ -5,6 +5,7 @@
  * Deprecate Pig support (CASSANDRA-10542)
  * Reduce contention getting instances of CompositeType (CASSANDRA-10433)
 Merged from 2.1:
+ * 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)
  * AssertionError: attempted to delete non-existing file CommitLog (CASSANDRA-10377)
diff --git a/src/java/org/apache/cassandra/db/index/SecondaryIndexManager.java b/src/java/org/apache/cassandra/db/index/SecondaryIndexManager.java
index 5edcf2e214..b0c31b6b7f 100644
--- a/src/java/org/apache/cassandra/db/index/SecondaryIndexManager.java
+++ b/src/java/org/apache/cassandra/db/index/SecondaryIndexManager.java
@@ -849,11 +849,14 @@ 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 ec2229ea91..3a626407c8 100644
--- a/src/java/org/apache/cassandra/service/StorageProxy.java
+++ b/src/java/org/apache/cassandra/service/StorageProxy.java
@@ -1633,7 +1633,7 @@ 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());
                 }
             }
         }