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Most adrenocortical neoplasms, renal cell carcinomas, and hepatocellular carcinomas are diagnosed by a combination of clinical and morphologic features. However, occasionally this histologic differential diagnosis requires additional ancillary tests, such as immunohistochemistry. The authors investigated the potential value of A103 in the differential diagnosis of these tumors. Thirty-two adrenocortical neoplasms, 86 renal cell carcinomas, and 57 hepatocellular carcinomas were evaluated by immunohistochemistry using a monoclonal antibody A103 and a standard ABC method. The adrenocortical neoplasms were 21 adenomas and 11 carcinomas. Thirty-one of the 32 adrenocortical neoplasms showed strong and diffuse granular cytoplasmic staining for Melan A. No nuclear reaction was observed. There were no differences in staining patterns between adrenocortical adenomas and carcinomas. With the exception of one clear cell renal cell carcinoma, all non-adrenocortical neoplasms were negative. The authors conclude that A103 is a useful addition to the immunohistochemical panel in the differential diagnosis of adrenocortical neoplasms from both renal cell and hepatocellular carcinomas. This marker, however, does not separate benign from malignant adrenocortical neoplasms.