Introduction: Malignant Peripheral Nerve Sheath Tumors (MPNSTs) account for 10% of all soft tissue sarcomas. More commonly associated with major nerve trunks such as the sciatic and sacral nerves, they are very rare in the upper extremity. When they are present, they usually involve the brachial plexus trunk. We hereby report a case of MPNST that presented as a ganglion cyst in the wrist. Case: A 43-year-old right hand dominant craftswoman presented with a one-year history of a slowly enlarging 1.5 X 2 cm mass located on the right hypothenar eminence. Surgical excision and pathologic evaluation revealed the tumor to be an MPNST. Over 48 months later, she is symptom-free, with no palpable mass or evidence of metastasis. Conclusion: This case represents a sporadic presentation of MPNST and the first of its kind in the hand, no reported cases are found in the literature. The hand surgeon should be aware that MPNST can present in the hand and awareness and familiarity with this rare entity will lead to more confidence in managing these tumors.