While diverse oncoproteins can activate specific STATs and constitutively-activated STAT signaling directly contributes to oncogenesis, many questions remain to the function of STATs in oncogenesis. For example the role of STAT1 and STAT3 for colorectal carcinoma (CRC) development and progression is controversial. The Moriggl tam and co-workers evaluated 414 CRC patient samples on tissue microarrays for differential expression of STAT1 and STAT3 protein levels and correlated ratios with clinical parameters. In addition we explored effects of STAT expression in cell lines and Xenografts. Two characteristic STAT1/3 expression patterns with opposite growth behavior could be distinguished: cell lines with a low STAT1/high STAT3 ratio showed faster tumor growth in xenografts. In contrast, xenografts of cell lines showing high STAT1 and low STAT3 levels grew slower. Importantly, these ratios reflected clinical outcome in CRC patients as well. We conclude that the ratio of STAT1 to STAT3 expression is a key determinant of CRC progression and that STAT1 counteracts pro-tumorigenic STAT3 signaling. Thus, we suggest that the STAT3/STAT1 ratios are better clinical predictors in CRC as compared to STAT3 or STAT1 levels alone.