Diffuse sclerosis variant of papillary thyroid carcinoma (DSVPTC) is an unusual malignant neoplasm that typically permeates the entire gland resulting in diffuse thyroid enlargement. In the absence of a dominant nodule, DSVPTC can be histologically deceiving because of exuberant inflammation and the scattered distribution of the microscopic tumor islands. The difficulty in diagnosing this tumor is compounded by its rarity and unusual clinical and histologic features. Herein, we describe a unique case of DSVPTC that was clinically masked by a co-existing second diffuse thyroid process--Graves' disease (GD). A subtotal thyroidectomy was performed in a 27-yr-old Caucasian female who presented with symmetrical diffuse thyromegaly with neck compressive symptoms, thyrotoxicosis, and biochemical signs of GD. Histologic examination of the thyroid gland unexpectedly revealed extensive involvement by DSVPTC in addition to the diffuse hyperplastic non-malignant thyroid follicles. This report illustrates the histologic features as well as the diagnostic challenge encountered in a rare simultaneous occurrence of DSVPTC and GD.<P>