Rationale: Marjolin’s ulcer (MU) is a rare skin malignancy derived from a chronic wound. Pressure ulcer related MU possesses poor prognosis and high metastatic rate, and it is difficult to be differentiated, especially when superimposed infection. Patient concerns: Here we report a case with pressure ulcer related MU which presented as necrotizing soft tissue infection (NSTI) to demonstrate the manifestation, treatment, and prognosis of this rare disease. Diagnoses: A 45-year-old male patient had spinal cord injury at age 2 years. He presented ischial pressure sore complicated with NSTI initially. After serial debridements and antibiotic treatment, the infection subsided. For the persistent verruca-like skin lesion, he underwent wide excision which revealed well-differentiated squamous cell carcinoma. Further image studies showed localized residual tumor without distant metastasis. Interventions: He then underwent hip disarticulation and anterior thigh fillet flap reconstruction. Local recurrence developed 3 months later, and re-wide excision and inguinal lymph node dissection were performed. No lymph node metastasis was noted and adjuvant radiotherapy was given. Outcomes: He was followed for 34 months and no recurrence or metastasis was found. The patient can move with a wheelchair or a hip prosthesis, and is partially dependent for daily activities. Lessons: MU can masquerade as NSTI and one should be alert to its malignant potential. Due to its aggressive nature, limb sacrifice can be considered in circumstances of profound involvement. As for the reconstruction method, pedicled fillet flap provided good wound coverage.