The functional relevance of squamous trans-differentiation in pancreatic cancer was unclear until recently, when studies from several laboratories, including our own, demonstrated that the transcription factor p63 (ΔN isoform, hereafter referred to as p63 for simplicity) is the master regulator of the adenosquamous phenotype in PDA (Andricovich et al., 2018; Hamdan and Johnsen, 2018; Somerville et al., 2018). The gene discussed is TP63; the disease is pancreatic neoplasm.