The histologic diagnosis of chromophobe renal cell carcinomas is often uncertain because of phenotype overlap among different types of kidney cancers. Recently, in a novel genetic classification of renal cell tumors, a combination of monosomies of chromosomes 1, 2, 3, 6, 10, 13, 17, and 21 have been suggested to have a diagnostic value for this unique type of tumor. Therefore, we have analyzed fresh and paraffin-embedded tissues obtained from 42 chromophobe renal cell carcinomas for allelic losses at the above-mentioned chromosomal regions by employing microsatellite markers. Loss of chromosomes 1, 2, 6, 10, 13, and 17 was detected in between 75% and 95% of tumors, and loss of chromosome 21 was observed in 54% of cases. All but one tumor showed a combination of monosomies at the specific chromosomes. Thus, applying the set of microsatellite markers used in this study, a PCR-based diagnosis of chromophobe renal cell carcinomas could be established within 1 to 2 days. The general applicability of this approach to fresh and paraffin-embedded tissues allows a correct genetic characterization in all cases where a diagnosis based on histopathology remains uncertain.