Rationale:Liposarcoma is an uncommon malignant tumor that develops in the fatty tissue; thus, the long-term follow-up results of extremely large liposarcomas in the submuscular layer of the thigh have rarely been reported. Here we share the course and outcome of 2 cases of a huge deep-seated liposarcoma in the thigh.Patient concerns:Two patients visited our clinic, each with a deep-seated mass in the thigh. First, a 44-year-old man presented to the outpatient clinic with a left thigh mass. Approximately 1 year later, an 80-year-old man presented to the outpatient clinic with a right posterior thigh mass.Diagnosis:Magnetic resonance imaging revealed an approximately 14 × 8 × 21 cm well-differentiated liposarcoma between the sartorius and iliopsoas muscle and an approximately 14 × 12 × 31.5 cm lipomatous mass in the posterior compartment of the right thigh involving the right adductor muscles. After complete marginal resection, an excisional biopsy was performed to confirm the diagnosis.Interventions:Both patients underwent complete marginal resection without chemotherapy or radiotherapy.Outcomes:A biopsy showed a 20 × 17 × 7 cm well-differentiated, well-encapsulated liposarcoma in the 44-year-old man and a 30 × 17 × 10 cm well-differentiated liposarcoma in the 80-year-old man. These patients have achieved approximately 61 and 44 months of recurrence-free survival to date, respectively.Lessons:Here we described the long-term outcomes of 2 patients with a huge deep-seated liposarcoma in the lower extremity. Complete marginal excision of well-differentiated liposarcoma can achieve excellent recurrence-free survival.