BACKGROUND The papillary variant of renal cell carcinoma has distinctive pathologic and clinical features. Because the prognosis of patients with papillary renal cell carcinoma differs from that of patients with other variants of renal cell carcinoma, accurate diagnosis based on cytologic material may be important for appropriate clinical disease management. METHODS A retrospective analysis of cytologic material from 17 papillary renal cell carcinomas and 52 other renal neoplasms with histologic follow-up was performed to identify the relative sensitivity and specificity of different cytologic criteria for papillary carcinoma. RESULTS Foamy macrophages and intracytoplasmic hemosiderin were the most sensitive and most specific criteria for the diagnosis of papillary renal cell carcinoma. Foamy macrophages were present in 14 of 17 cases (82%), and intracytoplasmic hemosiderin was present in 13 of 17 cases (76%). Foamy macrophages and intracellular hemosiderin were each present in only 2 of 52 (4%) of nonpapillary tumors examined. Malignant cells were arranged in papillary groups with fibrovascular cores in only 6 of 17 cases (35%), including only 1 of 7 high grade tumors. Nuclear grooves were present in 9 of 17 cases (53%) but were common in only 2 cases. Psammoma bodies were present in only 1 case. Nucleoli and pleomorphism were prominent in high grade tumors. These features, in association with frequent abundant vacuolated cytoplasm, made it difficult to distinguish high grade papillary carcinoma from the clear cell variant of renal cell carcinoma. However, as with low grade tumors, the presence of intracytoplasmic hemosiderin and foamy macrophages were important clues to the diagnosis of 6 of 7 high grade tumors (86%). CONCLUSIONS Intracytoplasmic hemosiderin and foamy macrophages are the most sensitive and specific markers for both high and low grade papillary renal cell carcinoma, and they allow for the correct diagnosis in most cases.