The molecular genetic correlates of a recently proposed subclassification of papillary renal cell carcinoma (PRCC) that designates tumors as type 1 and type 2 based on histological features have not yet been established. Alterations of known genes in PRCC include missense mutations in the MET oncogene (7q31) and rare translocations fusing TFE3 at Xp11.2 with a variety of other loci. Previous cytogenetic and allelic loss studies of PRCC cases revealed gain of chromosome 3q, 7, 8, 12q, 16, 17, and 20q, and loss of 1p, 6q, 9p, 11p, 13q, 14q, 18, 21q, X, and Y. We analyzed a series of sporadic type 1 and type 2 PRCC cases for MET mutations, TFE3 rearrangements, and allelic imbalance (AI) on 3p, 6, 7q, 9p, 11, 13q, 14q, 17q, 18, 20q, and 21q and compared selected results with a series of conventional renal cell carcinomas. A somatic mutation M1149T was identified in MET exon 17 in 1 of 35 PRCC cases whereas TFE3 rearrangements were not detected in 22 PRCC cases examined. Significant differences in AI frequency between PRCCs and conventional renal cell carcinoma cases were seen on 3p (37.5% versus 77.8%, P = 0.01), 7q (42.9% versus 5.6%, P = 0.01), and 17q (54.5% versus 20.0%, P = 0.03). Significant differences in AI frequency between type 1 and type 2 PRCCs were noted on 17q (78.6% versus 12.5%, P = 0.006) and 9p (0% versus 37.5%, P = 0.02). Additional analyses suggested that the relationship between 17q AI and PRCC type may be independent of histological grade and stage. Our findings identify genetic differences between the recently proposed type 1 and type 2 PRCCs, and support the premise that these subtypes arise from distinct genetic pathways.