Marjolin`s ulcer is a malignant lesion, which arises in a chronic wound. When squamous cell carcinoma occurs in Marjolin`s ulcer, the prognosis is known to be worse than that of cutaneous squamous cell carcinoma, due to other etiologies. A 56-year-old male who was diagnosed as chronic osteomyelitis was recommended for a surgical amputation of the left lower leg. After amputation, the histology of chronic ulcer revealed squamous cell carcinoma. In a few months period, multiple suppurative ulcers and nodules appeared near the amputation stump, as well as the proximal sites of the left leg, which appeared to spread rapidly. Biopsy of a representative lesion and positron emission tomography-computed tomography revealed a metastatic squamous cell carcinoma and malignant lymphadenopathy. Aggressive amputation without appropriate preoperative evaluation to detect the locoregional metastasis may be an inadequate option of the treatment for the patient due to a rapid spread of cancer metastasis, which may happen immediately after an amputation. Therefore, it is important to obtain a thorough preoperative evaluation of recalcitrant ulcer from osteomyelitis before the decision to undergo an amputation.