More than half of all human cancers carry p53 gene mutations whose resulting proteins are mostly full-length with a single amino acid change, abundantly present in cancer cells and unable to exert oncosuppressor activities. Frequently, mutant p53 proteins gain oncogenic functions through which they actively contribute to the establishment, the maintenance and the spreading of a given cancer cell. Intense research effort has been devoted to the deciphering of the molecular mechanisms underlying the gain of function of mutant p53 proteins. Here we mainly review the oncogenic transcriptional activity of mutant p53 proteins that mainly occurs through the aberrant cooperation with bona-fide transcription factors and leads to either aberrant up-regulation or down-regulation of selected target genes. Thus, mutant p53 proteins are critical components of oncogenic transcriptional networks that have a profound impact in human cancers.