Background: The c-Myb transcription factor is essential for maintenance of stem-progenitor cells in colon epithelia and its expression is deregulated in premalignant adenomatous polyps and colorectal carcinomas. Patients with colorectal carcinoma exhibiting upregulated c- Myb expression have poor prognosis. This can result from low sensitivity of cancer cells to cytotoxic agents. Methods: In our study, increased resistance of colon carcinoma CT26 and HCT116 cells overproducing exogenous c-Myb to cytotoxic agents was observed. These cells lost sensitivity to cisplatin and doxorubicin upon upregulation of c-Myb. The effect of c-Myb can be mediated by the mitogen-activated protein kinase (MAPK) signaling since phosphorylation of the MAPKs p38 and JNK was enhanced in cells exhibiting high expression of exogenous c-Myb. Results: To determine functional contribution of these kinases to resistance of the c-Myb-overexpressing cells to cisplatin, we used BIRB796 to inhibit activity of p38 and SP600125 to inhibit JNK. We found that the c-Myb-induced resistance of CT26 cells to cisplatin can be reversed by BIRB796. Conclusions: This result documents that it is the p38 kinase that mediates the effects of c-Myb on sensitivity of colon cancer CT26 cells to cisplatin (This study was supported by grant NT13441/2012 of the Internal Grant Agency of the Ministry of Health, Czech Republic).