Hydroxychloroquine (HXQ) sulphate is a synthetic antimalaria drug that is widely used in rheumatology due to its immunosuppressive properties. Delayed-type sensitization to this drug is rare. A 47-year-old woman diagnosed with HLA B27 ankylosing spondylitis was treated with HXQ for 22 days and had to discontinue the drug due to gastric intolerance. Five days later the patient developed erythema multiforme (EM) with an extensive and unusual distribution. Patch test with 10% HXQ in DMSO were positive at 48 hours. Eight days later a generalized pruriginous erythematous papular exanthema developed, and a skin biopsy was obtained. The first reaction was EM. Patch-testing elicited systemic eczematous contact dermatitis. We report two different clinical patterns of delayed hypersensitivity in the same patient and with the same drug.