Background:  Porokeratosis (PK) represents a heterogeneous group of disorders of keratinization and has a wide variety of clinical manifestations. PK may exhibit similarities with psoriasis at both clinical and molecular levels. The genetic basis and pathogenesis for PK remain elusive.Methods:  We studied the transcriptional profiles of three pairwise lesional and uninvolved skin biopsies from patients with different subtypes of PK using the Illumina® BeadArray™ platform.Results:  A total of 37 upregulated genes were identified in our study, including wound‐induced keratins, S100 calcium‐binding protein genes involved in epidermal differentiation, as well as genes involved in mediating intercellular communication and the immune response. To our knowledge, this is the first study that characterizes the immune profile of PK lesions.Conclusions:  Here, we report that keratinocytes (KCs)‐harboring lesions have activated and overexpressed wound‐induced keratin genes, which appear to be coregulated with other genes involved in mediating epidermal differentiation, intercellular communication and immunity. This study, from the perspective of gene profiling, supports that gene misregulation in PK mimics that of psoriasis. Our data indicate that the genes implicated in the T‐cell‐mediated immune response pathway and activation of KCs play a key role in the pathogenesis of PK.