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Lupus erythematosus tumidus (LET) is a subset of cutaneous lupus erythematosus that generally presents with urticaria-like papules and plaques located on sun-exposed areas. Systemic treatment with antimalarials, especially hydroxychloroquine (HCQ), is the first-line systemic therapy for LET. Even if these drugs have a safe profile, side effects such as retinal toxicity, maculopapular rash, gastrointestinal upset, hemolytic anemia and blue-gray discoloration of the skin or the mucous membranes, have been rarely reported in the literature. Herein, we describe a rare case of a 46-year-old smoking woman with LET who developed a generalized myopathy after HCQ treatment.