Genes of the myc family are frequently overexpressed in lung cancer. Gene amplification can explain the deregulation of these genes in a subset of tumors and cell lines, but in most cases, the cause of the elevated myc expression remains unknown. We examined whether messenger RNA (mRNA) stabilization could be contributing to myc gene overexpression in lung cancer cell lines. The decay pattern of c-myc or N-myc mRNA was analyzed in 11 such cell lines and in unimmortalized human embryonic lung cells. Eight lung cancer cell lines showed stabilization of c-myc or N-myc transcripts. To determine whether this stabilization was unique to myc genes, the decay pattern of the unstable c-fos proto-oncogene mRNA was also studied. The same cell lines that exhibited stabilization of myc mRNA showed an abnormally slow decay of the c-fos message, suggesting that there might be a correlation between the abnormal decay of c-fos and myc transcripts. In contrast, the half-life of histone 2B mRNA, which is degraded in a cell cycle-specific manner, did not appear to correlate with that of myc and fos. Our results suggest that an mRNA decay pathway responsible for the destruction of unstable proto-oncogene mRNAs may be commonly affected in lung cancers.