Zoledronic acid, an amino-bisphosphonate, is an antiresorptive drug given intravenously. It is commonly used for the treatment of severe postmenopausal osteoporosis, and it is also used for other types of osteoporosis, management of bone metastasis, multiple myeloma, hypercalcemia, and Paget's disease. The use varies according to these diseases. The drug is usually well-tolerated with the most common side effects being acute-phase reactions with weakness and musculoskeletal pain as well as gastrointestinal effects. However, the increase in usage of zoledronic acid has produced rare reports of side effects, such as atrial fibrillation, atypical fracture, delayed fracture healing, osteonecrosis of the jaw, or buccal or genital mucosa. Less common cutaneous side effects associated with zoledronic acid include fever rash, maculopapular lesions, keratitis, dermatitis, B-cell pseudolymphoma, skin erythema multiform, and vasculitis. Although these cutaneous reactions are generally mild and self-limiting, others can be severe such as toxic epidermal necrolysis and pancytopenia. We hereby describe a case of diffuse skin adverse reactions, a type of confluent erythematous macules in the trunk and arms with extended petechial macules along the left thigh and leg, induced 2 days after the administration of zoledronic acid for primary osteoporosis in a 53-year-old woman, without any allergic context or other associated drugs taken.