Vitamin D and calcium have long been known to regulate differentiation and proliferation of keratinocytes. However, the role of parathyroid hormone (PTH) in keratinocyte differentiation is yet to be elucidated. PTH is a classical endocrine hormone that was first identified more than 80 years ago as a key regulator of blood calcium levels. Serum PTH is a sensitive indicator of calcium and vitamin D deficiency. Recently it was reported that serum intact-PTH (iPTH) and a genetic polymorphism in Pth are important for skin tumor resistance. Higher iPTH levels have been detected in sera from cancer-resistant MSM/Ms mice compared with susceptible FVB/NJ mice. Skin carcinogenesis experiments with MSM-BAC transgenic mice (Pth^MSM-Tg) and Pth heterozygous knockout mice (Pth^+/-) showing higher amounts of iPTH in sera conferred stronger resistance to skin tumors. In this report, it is also shown that PTH increases intracellular calcium in keratinocytes and promotes their terminal differentiation.