To investigate the prognostic value of multiple genetic alterations, individual molecular tumor profiles were established in 79 sporadic colorectal carcinomas (41 stage II and 38 stage III). Tumors were analyzed for allelic loss (LOH) and genetic instability (MSI) using 14 microsatellites intragenic to or associated with tumor suppressor or DNA mismatch repair genes. Molecular profiling identified tumors with LOH at multiple loci without microsatellite instability (MSS), tumors with high levels of LOH and low level microsatellite marker instability (MSI-L), and tumors with high levels of MSI (MSI-H), but rare LOH. K-ras mutations occurred more frequently in MSS/MSI-L carcinomas (26%) than in MSI-H colorectal tumors (10%), the latter showing a high frequency of TGFbeta type II frameshift mutations (82%). Correlation of molecular and clinical data revealed a better prognosis for stage III tumor patients displaying 5q12 loss rather than retention of heterozygosity. Thus, molecular profiling allows the identification of new prognostic markers and might facilitate the stratification of colorectal cancer patients.