diff --git a/augur/frequencies.py b/augur/frequencies.py
index 57db3052e..a1dd3b572 100644
--- a/augur/frequencies.py
+++ b/augur/frequencies.py
@@ -8,7 +8,7 @@
 from Bio.Align import MultipleSeqAlignment
 
 from .frequency_estimators import get_pivots, alignment_frequencies, tree_frequencies
-from .frequency_estimators import AlignmentKdeFrequencies, TreeKdeFrequencies
+from .frequency_estimators import AlignmentKdeFrequencies, TreeKdeFrequencies, TreeKdeFrequenciesError
 from .utils import read_metadata, read_node_data, write_json, get_numerical_dates
 
 
@@ -162,7 +162,12 @@ def run(args):
                 include_internal_nodes=args.include_internal_nodes,
                 censored=args.censored
             )
-            frequencies = kde_frequencies.estimate(tree)
+
+            try:
+                frequencies = kde_frequencies.estimate(tree)
+            except TreeKdeFrequenciesError as e:
+                print("ERROR: %s" % str(e), file=sys.stderr)
+                return 1
 
             # Export frequencies in auspice-format by strain name.
             frequency_dict = {"pivots": list(kde_frequencies.pivots)}
diff --git a/augur/frequency_estimators.py b/augur/frequency_estimators.py
index 6bc3014b7..54eaede65 100644
--- a/augur/frequency_estimators.py
+++ b/augur/frequency_estimators.py
@@ -12,6 +12,12 @@
 log_thres = 10.0
 
 
+class TreeKdeFrequenciesError(Exception):
+    """Represents an error estimating KDE frequencies for a tree.
+    """
+    pass
+
+
 def get_pivots(observations, pivot_interval, start_date=None, end_date=None):
     """Calculate pivots for a given list of floating point observation dates and
     interval between pivots.
@@ -1143,6 +1149,13 @@ def estimate(self, tree):
                 for key, value in self.weights.items():
                     self.weights[key] = value / weight_total
 
+            # Confirm that one or more weights are represented by tips in the
+            # tree. If there are no more weights, raise an exception because
+            # this likely represents a data error (either in the tree
+            # annotations or the weight definitions).
+            if len(self.weights) == 0:
+                raise TreeKdeFrequenciesError("None of the provided weight attributes were represented by tips in the given tree. Doublecheck weight attribute definitions and their representations in the tree.")
+
             # Estimate frequencies for all tips within each weight attribute
             # group.
             weight_keys, weight_values = zip(*sorted(self.weights.items()))
diff --git a/tests/python3/test_frequencies.py b/tests/python3/test_frequencies.py
index c2f653cff..6f483074e 100644
--- a/tests/python3/test_frequencies.py
+++ b/tests/python3/test_frequencies.py
@@ -12,7 +12,7 @@
 # we assume (and assert) that this script is running from the tests/ directory
 sys.path.append(str(Path(__file__).parent.parent.parent))
 
-from augur.frequency_estimators import get_pivots, TreeKdeFrequencies, AlignmentKdeFrequencies
+from augur.frequency_estimators import get_pivots, TreeKdeFrequencies, AlignmentKdeFrequencies, TreeKdeFrequenciesError
 from augur.utils import json_to_tree
 
 # Define regions to use for testing weighted frequencies.
@@ -173,6 +173,19 @@ def test_weighted_estimate_with_unrepresented_weights(self, tree):
         # Frequencies should sum to 1 at all pivots.
         assert np.allclose(np.array(list(frequencies.values())).sum(axis=0), np.ones_like(kde_frequencies.pivots))
 
+        # Estimate weighted frequencies such that all weighted attributes are
+        # missing. This should raise an exception because none of the tips will
+        # match any of the weights and the weighting of frequencies will be
+        # impossible.
+        weights = {"fake_region_1": 1.0, "fake_region_2": 2.0}
+        kde_frequencies = TreeKdeFrequencies(
+            weights=weights,
+            weights_attribute="region"
+        )
+
+        with pytest.raises(TreeKdeFrequenciesError):
+            frequencies = kde_frequencies.estimate(tree)
+
     def test_only_tip_estimates(self, tree):
         """Test frequency estimation for only tips in a given tree.
         """