Plantar heloma is a keratotic disorder that can be described as a circumscribed area of thickening with a central core that may penetrate the dermis. Although often considered a minor complaint, longstanding lesions can be debilitating and severely impact on person's quality of life. We present the first retrospective case series at long-term follow-up about the use of plantar lipofilling as a treatment for metatarsalgia caused by plantar heloma. Six patients affected by plantar heloma associated to external metatarsalgia underwent plantar lipofilling. The surgical session was performed as an outpatient procedure. Clinical evaluation was performed using the AOFAS lesser metatarsophalangeal-interphalangeal (MTP-IP) score. Mean AOFAS lesser MTP-IP score improved from a preoperative score of 66.6 ± 3.2 points (range 47-77 points) to a post-operative score of 92.8 ± 2.7 points (range 86-95 points); all patients were satisfied with the outcome at the final follow-up. Post-operative clinical examination at final follow-up showed an increase in thickness of the subcutaneous layer and a decrease of dermal layer thanks to the supporting and trophic action of fat cells. Plastic regenerative procedures applicated to a typical foot and ankle surgery field, such as metatarsal overloading, metatarsalgia and forefoot problems, should be encouraged to allow new treatment horizons.