Cytogenetic deletions and loss of heterozygosity (LOH) at certain restriction fragment length polymorphic (RFLP) loci on the short arm of chromosome 3 occur in most nonpapillary clear cell variants of renal cell carcinoma (RCC). Studies of other variants of renal cell carcinomas are sparse and inconclusive. We investigated the LOH at three of the most commonly deleted loci on the short arm of chromosome 3 in 50 neoplasms representing the histopathologic spectrum of renal cortical neoplasms by polymerase chain reaction (PCR)-based restriction fragment length polymorphism assay and Southern blotting analysis. Our results indicate that PCR-based RFLP analysis accurately identified the LOH on the short arm of chromosome 3 in the different histopathologic variants of renal neoplasms. LOH was observed at D3F15S2 locus (3p21 telomeric) in >60% of nonpapillary renal cell carcinomas. In contrast. 1 of 6 papillary renal cell carcinomas showed LOH at D3S32 locus (3p21 centromeric), and one of seven oncocytomas demonstrated LOH at D3F15S2 locus. We also report that 1 of 3 collecting duct carcinomas showed LOH at D3S32 locus. In this series there was no correlation between LOH, histologic grade, tumor stage, and DNA content. We conclude that (a) LOH on 3p is not restricted to the clear cell type of RCC, lb) the most common LOH were telomeric to D3S32 locus at the 3p21 region, and (c) no statistical correlation between the LOH at 3p and histologic grade. DNA ploidy, or clinical stage was found in this series.