The c‐mos proto‐oncogene product, Mos, is a serine/threonine kinase that can activate ERK1 and 2 mitogen‐activated protein (MAP) kinases by direct phosphorylation of MAPK/ERK kinase (MEK). ERK activation is essential for oncogenic transformation of NIH 3T3 cells by Mos. In this study, we examined how mitogenic and oncogenic signalling from the Mos/MEK/ERK pathway reaches the nucleus to activate downstream target genes. We show that c‐Fos (the c‐fos protooncogene product), which is an intrinsically unstable nuclear protein, is metabolically highly stabilized, and greatly enhances the transforming efficiency of NIH 3T3 cells, by Mos. This stabilization of c‐Fos required Mos‐induced phosphorylation of its C‐terminal region on Ser362 and Ser374, and double replacements of these serines with acidic (Asp) residues markedly increased the stability and transforming efficiency of c‐Fos even in the absence of Mos. Moreover, activation of the ERK pathway was necessary and sufficient for the c‐Fos phosphorylation and stabilization by Mos. These results indicate that c‐Fos undergoes stabilization, and mediates at least partly the oncogenic signalling, by the Mos/MEK/ERK pathway. The present findings also suggest that, in general, the ERK pathway may regulate the cell fate and function by affecting the metabolic stability of c‐Fos.