The most common genetic aberration seen in nonpapillary renal cell carcinoma is believed to be the loss or inactivation of allelic material on the short arm of chromosome 3 (3p). Two patients underwent nephrectomy at our institution, each initially receiving a histologic diagnosis of renal cell carcinoma. Molecular analysis of these tissues revealed no genetic deletion on 3p, prompting further histologic and immunohistochemical evaluation of the original specimens. These additional studies confirmed alternate histologies other than renal cell carcinoma in each case. These data suggest that the loss of genetic material on the short arm of chromosome 3 may be specific for nonpapillary renal cell carcinoma. Molecular analysis may prove to be a useful adjunct in establishing the diagnosis in renal neoplasms with equivocal histologies.