Multilocular cystic renal cell carcinoma (MCRCC) is an uncommon variant of renal neoplasm and its histogenesis is unclear. The aim of this study was to use immuno- and lectin histochemistry to delineate histochemical patterns which might indicate the histogenetic origin of MCRCC from a particular part or parts of the nephron. We present our experience with nine cases of MCRCC. Fifteen cases of renal cell carcinoma with cystic degeneration (RCC-CD) were selected for comparison with MCRCC. We carried out clinicopathological and immunohistochemical examinations of the MCRCC cases. Clinically, the prognosis of the patients was quite good, in that all nine patients are alive and without recurrence at the time of this report. The MCRCCs reacted strongly in a higher proportion of cases with the distal nephron markers, such as peanut agglutinin (PNA, 88.9%) and MUC1–core antibody (MUC1, 100%), but none reacted preferentially with proximal nephron markers such as vimentin, Leu M1 and Lotus tetragonolobus (LTA). The RCC-CD tumours reacted with vimentin (40%), Leu M1 (66.7%) and LTA (86.7%). Except for two cases, the RCC-CD tumours did not react with PNA or MUC1 core antibody. These results illustrate the different patterns of expression of MCRCC and RCC-CD and suggest that MCRCC originates from the distal nephron. Therefore, MCRCC should be differentiated from other types of renal cell carcinoma on the basis of the histogenesis of the tumour and the clinicopathological findings.