Background Keratinocyte (KC) apoptosis is believed to play an important role in the pathogenesis of spongiotic dermatitis, in particular for the formation of spongiosis. Objective To investigate changes in the expression level of the apoptosis regulatory proteins cleaved caspase-3, Fas, Bcl-2, nuclear factor κB (NF-κB) and p53 in skin samples of patients with spongiotic dermatitis. Patients and methods The present study included a total of 50 patients with spongiotic dermatitis and 10 healthy controls. Patients were classified into five groups (10 patients each): group A, atopic dermatitis; group B, allergic contact dermatitis; group C, irritant contact dermatitis; group D, nummular eczema; and group E, dyshidrotic eczema. Using immunohistochemistry, we investigated the expression of apoptotic regulatory proteins cleaved caspase-3, Fas, Bcl-2, NF-κB and p53 in skin biopsies taken from all patients and controls. Results The mean values of cleaved caspase-3 and Fas expression were statistically increased in patients with acute spongiotic dermatitis compared with the controls (P