Programmed cell death 4 (Pdcd4) is a tumor suppressor frequently lost in tumors of various origins thus contributing to tumor progression. Expression of Pdcd4 in melanoma, however, has not been extensively studied to date.Pdcd4 protein levels were assessed in 23 human melanoma cell lines and in normal melanocytes by western blot analysis. Also, effects of LY294002, rapamycin and PD098059 on Pdcd4 protein levels were analyzed.Pdcd4 is suppressed in ~25% of human cell lines established from advanced melanoma lesions. Pdcd4 protein levels in melanoma cells were up-regulated by treatment with inhibitors of Akt signaling, one of the key pathways leading to Pdcd4 suppression, and to a lesser extent by inhibiting MEK/ERK pathway.Pdcd4 loss is not a common event in melanoma progression yet suppression of Pdcd4 defines a subset of melanoma cells and can be used for molecular typing of melanoma. Our results help determine the significance of Pdcd4 loss in melanoma as well as its up-regulation by Akt pathway inhibitors, which are promising tools in melanoma treatment.