Renal cell carcinoma (RCC) is one of the most frequent malignancies in Western societies. The most common subtypes are conventional (clear-cell) and papillary carcinomas, which account for about 75 and 10% of cases, respectively. Cytogenetically, conventional RCC is the best-studied subtype and is characterized by chromosomal losses: loss of the short arm of chromosome 3 being the most common. Papillary tumors frequently show gains of chromosomes 7 and 17, and the more progressed forms have, in addition, gains of chromosomes 16, 12, and 20. In the present investigation we used 796 RCC karyotypes to identify the most frequent genomic imbalances. Tumor cases were then classified with respect to the presence or absence of these imbalances and statistically analyzed to assess the order of appearance of chromosomal imbalances, as well as possible karyotypic pathways and cytogenetic subtypes. We established a temporal order by which the different imbalances occur and showed that at least two cytogenetic pathways exist in RCC, one hypodiploid characterized by presence of 3p- and one hyperdiploid characterized by the presence of +7. The data suggest that conventional-type tumors predominantly evolve through the hypodiploid pathway but that an alternative route may be by hyperdiploidy if 3p- is present. Tumors with a papillary growth pattern predominantly progress through the hyperdiploid pathway. The analyses also revealed three possible cytogenetic subtypes of the papillary tumors, one characterized by the presence of +10, a second by +17 and +3q, and a third by +16, +20, and +12.