Recent data indicate that distinct skin areas show different microbial/chemical milieu. Keratinocytes (KC) respond to these stimuli by producing cytokine mediators. Therefore, we aimed to determine KC‐derived cytokine expression in distinct healthy skin regions (gland‐poor GP, sebaceous gland‐rich SGR and apocrine gland‐rich AGR), and their changes in skin diseases of the given regions (atopic dermatitis AD, papulopustular rosacea PPR and psoriasis). Cytokines were analysed at the mRNA and protein levels, and literature analysis was performed for functional categorization. The three regions showed characteristically different cytokine patterns. GP was featured by an IL‐25/IL‐33/IL‐36RA/IL‐38/IL‐18 cytokine milieu, SGR was characterized by IL‐23/IL‐17C/IL‐18, and AGR skin exhibited a mixed IL‐25/IL‐33/IL‐23/IL‐18 profile. Literature analyses revealed different homeostatic and proinflammatory roles of these cytokine patterns (Th2 related in GP, Th17 related in SGR and mixed Th2/Th17 in AGR). In skin diseases which are primarily epidermal cytokine‐driven (AD, PPR), the level of the regionally characteristic cytokines were further elevated, in contrast to the autoantigen‐driven psoriasis, where the cytokine pattern was independent from the localization. Healthy skin regions are equipped with different KC‐derived cytokine profiles, which may influence each region's capability of mediator production in certain types of dermatoses.