Background <p>Pancreatic panniculitis is a rare form of lobular panniculitis characterized by subcutaneous fat necrosis occurring at cutaneous sites distant from the pancreas. It is most often associated with pancreatitis, while pancreatic malignancies — dominated by acinar cell carcinoma — represent a minority of cases. Recognizing this cutaneous manifestation is important, as it may be the primary and sole manifestation of an underlying pancreatic neoplasm.</p> Case presentation <p>A 79-year-old female presented with a one-month history of painful subcutaneous nodules of the lower limbs without abdominal pain, weight loss, or other symptoms. Laboratory workup revealed elevated serum lipase levels (&gt; 1000 U/L). Skin biopsy showed lobular panniculitis with characteristic “ghost cells”, consistent with pancreatic panniculitis. Abdominal imaging identified a 14-mm mass in the head of the pancreas and endoscopic ultrasound-guided fine-needle aspiration suggested a well-differentiated adenocarcinoma. Given the resectable nature of the tumor and a favorable geriatric assessment, the patient underwent total pancreatectomy, which confirmed a 25-mm well-differentiated pancreatic ductal adenocarcinoma staged pT2N2R0, followed by adjuvant chemotherapy with mFOLFIRINOX. The cutaneous lesions resolved within the first postoperative week.</p> Conclusions <p>Pancreatic panniculitis can be the sole manifestation of an underlying pancreatic malignancy; therefore, clinicians should consider this rare but important association. Serum lipase measurement should be included in the workup of any unexplained panniculitis, and pancreatic imaging should be promptly performed in case of high levels. Early recognition can lead to timely diagnosis and effective treatment.</p>