Patients receiving treatment for tuberculosis may experience an unexpected deterioration of their disease; this is known as a paradoxical reaction. We present the case of a 59-year-old man with lupus vulgaris who experienced a paradoxical deterioration of cutaneous lesions after starting antituberculosis therapy. The reaction was self-limiting; the lesions gradually improved, and the final outcome was very good. Paradoxical reactions are well-known in patients with human immunodeficiency virus (HIV) infection who start antiretroviral therapy, but they can also occur in non-HIV-infected patients with tuberculosis who start antituberculosis therapy. In the literature reviewed, paradoxical reactions involving skin lesions were described in patients with miliary tuberculosis. The case we report is the first of a paradoxical reaction in lupus vulgaris. The increasing frequency of tuberculosis in Spain could lead to a rise in the number of paradoxical reactions.