A family consisting of a mother and 2 daughters presented with the skeletal and cardiac changes (atrial septal defect) compatible with the Holt Oram Syndrome. The roentgenographic features of the upper limb abnormalities as well as other skeletal changes were quite extensive and variable. In addition, one 16 year old daughter developed an adenocarcinoma with a pseudo-adamantine pattern of the parotid gland. This represents the first known malignancy complicating this syndrome. Further investigation of families with this syndrome will determine whether or not this occurrence is coincidental.