Acquired ichthyosis (AI) is a clinical condition associated with keratinization defects, characterized by accumulation of cutaneous scales, with or without epidermal proliferation and inflammation of the dermis. With this report, we want to present the case of a 58-year-old man who referred to our clinic with severe and diffuse scaling of the skin associated with irrepressible itching, unresponsive to oral antihistamines. After our diagnosis of acquired ichthyosis, we subjected him to diagnostic investigations aimed at identifying the triggering cause. After performing laboratory tests and radiographic investigations, the diagnosis of pulmonary tuberculosis (TBC) emerged. The treatment of the underlying TBC initially did not improve the patient's clinical condition, but after the interruption of treatment with isoniazid, the cutaneous involvement resolved. In literature, to date, there is poor scientific evidence of tuberculosis-related and isoniazid-related ichthyosis; moreover, some of those patients had a concomitant history of solid tumors (long associated with acquired ichthyosis), which makes it more difficult to identify the triggering cause among many.