diff --git a/Modules/Core/Common/src/itkImageIORegion.cxx b/Modules/Core/Common/src/itkImageIORegion.cxx
index 8dddf9b9776..ee0eaddf1e9 100644
--- a/Modules/Core/Common/src/itkImageIORegion.cxx
+++ b/Modules/Core/Common/src/itkImageIORegion.cxx
@@ -190,25 +190,28 @@ ImageIORegion::IsInside(const IndexType & index) const
   return true;
 }
 
-/** Test if a region (the argument) is completely inside of this region */
+
+/** Test if a region (the argument) is completely inside of this region. If
+ * the region that is passed as argument has a size of value zero, or if the
+ * dimensionality is zero, then it will not be considered to be inside of the
+ * current region, even its starting index is inside. */
 bool
-ImageIORegion::IsInside(const Self & region) const
+ImageIORegion::IsInside(const Self & otherRegion) const
 {
-  IndexType beginCorner = region.GetIndex();
-
-  if (!this->IsInside(beginCorner))
+  if (m_ImageDimension == 0 || otherRegion.m_ImageDimension != m_ImageDimension)
   {
     return false;
   }
-  IndexType endCorner(region.m_ImageDimension);
-  SizeType  size = region.GetSize();
+  const auto & otherIndex = otherRegion.m_Index;
+  const auto & otherSize = otherRegion.m_Size;
+
   for (unsigned int i = 0; i < m_ImageDimension; ++i)
   {
-    endCorner[i] = beginCorner[i] + size[i] - 1;
-  }
-  if (!this->IsInside(endCorner))
-  {
-    return false;
+    if (otherIndex[i] < m_Index[i] || otherSize[i] == 0 ||
+        otherIndex[i] + static_cast<IndexValueType>(otherSize[i]) > m_Index[i] + static_cast<IndexValueType>(m_Size[i]))
+    {
+      return false;
+    }
   }
   return true;
 }
diff --git a/Modules/Core/Common/test/itkImageIORegionGTest.cxx b/Modules/Core/Common/test/itkImageIORegionGTest.cxx
index dd00dd84c3c..8af2a359f27 100644
--- a/Modules/Core/Common/test/itkImageIORegionGTest.cxx
+++ b/Modules/Core/Common/test/itkImageIORegionGTest.cxx
@@ -197,3 +197,22 @@ TEST(ImageIORegion, IsAssignable)
   Expect_Assignable(GenerateRandomRegion(2), GenerateRandomRegion(2));
   Expect_Assignable(GenerateRandomRegion(2), GenerateRandomRegion(3));
 }
+
+
+// Tests that a zero-sized region is not considered to be inside of another region.
+TEST(ImageIORegion, ZeroSizedRegionIsNotInside)
+{
+  for (const unsigned int dimension : { 0, 2, 3 })
+  {
+    itk::ImageIORegion region(dimension);
+
+    region.SetSize(itk::ImageIORegion::SizeType(dimension, 2));
+
+    for (const auto indexValue : { -1, 0, 1 })
+    {
+      itk::ImageIORegion zeroSizedRegion(dimension);
+      zeroSizedRegion.SetIndex(itk::ImageIORegion::IndexType(dimension, indexValue));
+      EXPECT_FALSE(region.IsInside(zeroSizedRegion));
+    };
+  }
+}