The most common genetic changes associated with lung cancer involve abnormalities of the genes that regulate the cell cycle. Molecular networking of P53 and P16 tumor suppressor genes and K-RAS oncogene exerts a crucial impact on cell cycle regulation and appears to be of major clinical significance for lung cancer evaluation. The present review article summarizes evaluations of P53, P16 and K-RAS in lung cancer with particular focus on biological and clinical implications, as well as on new molecular approaches to the study of these genes: P53 by yeast functional assay, P16 by methylation specific PCR (MSP) and K-RAS by enriched PCR technique.