diff --git a/CHANGELOG.md b/CHANGELOG.md
index cbcaea1a6..46965f0b8 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -9,6 +9,7 @@
 - Remove NaN values from band information ([#1414](../../pull/1414))
 - Add a singleBand option to the multi-source specification ([#1416](../../pull/1416))
 - Allow better detection of multiple file dicom ([#1417](../../pull/1417))
+- Better missing data detection from tifffile ([#1421](../../pull/1421))
 
 ### Changes
 - Remove an unused parameter in a private method ([#1419](../../pull/1419))
diff --git a/sources/tifffile/large_image_source_tifffile/__init__.py b/sources/tifffile/large_image_source_tifffile/__init__.py
index 4bf1e8ec2..c0e16d382 100644
--- a/sources/tifffile/large_image_source_tifffile/__init__.py
+++ b/sources/tifffile/large_image_source_tifffile/__init__.py
@@ -24,6 +24,13 @@
     pass
 
 
+class checkForMissingDataHandler(logging.Handler):
+    def emit(self, record):
+        msg = record.getMessage()
+        if 'Missing data are zeroed' in msg or 'OME series expected ' in msg:
+            raise TileSourceError(record.getMessage())
+
+
 def _lazyImport():
     """
     Import the tifffile module.  This is done when needed rather than in the
@@ -41,8 +48,13 @@ def _lazyImport():
             tifffile = None
             msg = 'tifffile module is too old.'
             raise TileSourceError(msg)
-        logging.getLogger('tifffile.tifffile').setLevel(logging.ERROR)
-        logging.getLogger('tifffile').setLevel(logging.ERROR)
+        # The missing data handler consumes most warnings, but throws if a
+        # warning about missing data occurs
+        # The tifffile.tifffile logger is in older versions of tifffile
+        logging.getLogger('tifffile.tifffile').setLevel(logging.WARNING)
+        logging.getLogger('tifffile.tifffile').addHandler(checkForMissingDataHandler())
+        logging.getLogger('tifffile').setLevel(logging.WARNING)
+        logging.getLogger('tifffile').addHandler(checkForMissingDataHandler())
 
 
 def et_findall(tag, text):
@@ -498,8 +510,6 @@ def getTile(self, x, y, z, pilImageAllowed=False, numpyAllowed=False, **kwargs):
             if sidx not in self._zarrcache:
                 if len(self._zarrcache) > 10:
                     self._zarrcache = {}
-                if self.frames > 1:
-                    series.keyframe.nodata = None
                 za = zarr.open(series.aszarr(), mode='r')
                 hasgbs = hasattr(za[0], 'get_basic_selection')
                 self._zarrcache[sidx] = (za, hasgbs)