<b><i>Introduction:</i></b> Subungual squamous cell carcinoma (sSCC) is the most frequent malignant tumor of the nail unit. When suspecting sSCC, accurate diagnosis is supported by nail biopsy. Depth of invasion and histopathologic signs of human papillomavirus (HPV) infection are related to an unfavorable prognosis. In this case, it is necessary to rule out bone invasion by radiography or MRI, and in case of doubt, amputation is indicated. <b><i>Case Presentation:</i></b> We present 2 cases of sSCC with a confirmatory biopsy of sSCC with HPV and invasion; in both cases, MRI was difficult to distinguish between bone invasion and bone marrow inflammation. Before amputating the distal phalanx, we decided to perform a bone biopsy during the excisional surgery. Neither case required amputation. <b><i>Conclusion:</i></b> We propose that when an invasive sSCC is present and an MRI is doubtful of bone invasion, before amputating, a bone biopsy should be performed.