Psoriasis is a multifactorial systemic disease with predominantly cutaneous manifestations. The role of tuberculosis infection in the pathogenesis of psoriasis has not been consistently proven. Current guidelines recommend screening for tuberculosis infection in any patient with psoriasis when the initiation of biologic therapy is being considered. Isoniazid is an antibiotic with high bactericidal effect on replicating mycobacteria and constitutes the most commonly prescribed treatment for latent tuberculosis infection. Here, we report two cases of patients with psoriasis who presented at our clinic with extensive cutaneous involvement despite previous treatments with topical and systemic therapies. Both were considered as candidates for biologic therapy. As part of the screening protocol, a tuberculin test was performed with a positive result. In the absence of symptoms and chest radiography findings, isoniazid 300 mg/day for 6 months was prescribed to treat latent tuberculosis infection. This resulted in significant clearing of their skin lesions in the absence of any other concurrent treatment, apart from emollients. Both patients remained clinically stable and with no need of further systemic treatment. This situation has only been described twice before in the English‐language published work. These cases highlight the possible role of tuberculosis infection in the pathogenesis of psoriasis, suggesting the possible existence of a link between untreated infection and skin lesions. This can lead to consideration of novel therapeutic strategies and new lines of investigation.