Background The 14-3-3 proteins are a family of conserved regulatory molecules expressed in all eukaryotic cells, which play essential roles in a wide range of vital regulatory processes, including differentiation, proliferation and transformation. In mammalian cells, seven 14-3-3 isoforms (, , epsilon, , /, sigma and ) have been identified, and each of these seems to have distinct tissue localizations and isoform-specific functions. 14-3-3 and 14-3-3 are two important members of the 14-3-3 family. Aim To explore the role of 14-3-3 and 14-3-3 in normal skin and psoriasis vulgaris (PV) skin. Methods Using immunohistochemistry and western blotting, we measured expression of 14-3-3 and 14-3-3 in 30 PV lesions and 15 normal skin samples. The average optical density (OD) of immunostaining and the relative grey scale of immunoblotting for 4-3-3 and 14-3-3 were analysed by the t-test. Results The average OD of immunostaining for 14-3-3 and 14-3-3 was 0.17 +/- 0.00 and 0.24 +/- 0.01, respectively, in psoriatic lesions, which was significantly lower than in normal controls (0.22 +/- 0.01 and 0.37 +/- 0.02, respectively; P<0.01 for both). There was also a significant difference in the relative grey scale of 14-3-3 and 14-3-3 (0.52 +/- 0.03 and 1.44 +/- 0.06, respectively) in psoriatic lesions compared with normal control tissue (3.32 +/- 0.15 and 2.76 +/- 0.11, respectively; P<0.01 for both). Conclusions Expression of 14-3-3 and 14-3-3 were lower in psoriatic lesions than in normal human skin tissue. We speculate that 14-3-3 and 14-3-3 may be involved in the regulation of normal skin function, thus decreased expression of 14-3-3 and 14-3-3 might precipitate the disturbance in proliferation and differentiation of keratinocytes seen in psoriasis.