Cutaneous scalp involvement as the initial manifestation of high-grade B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL), is rare and diagnostically challenging — particularly when a concurrent infectious illness produces overlapping systemic findings. We report a 58-year-old male from St. Kitts and Nevis with a history of diabetes mellitus type 2 who presented to the emergency department with tender scalp nodules and right periorbital papules. In the weeks prior, he had been hospitalized in St. Kitts with a leukemoid reaction (peak WBC 57,200/μL), fever, scleral icterus, and transaminitis, attributed to presumed Lyme disease and treated with IV ceftriaxone. On admission, examination revealed non-tender scalp nodules without erythema, bilateral cervical adenopathy, and hepatomegaly. Laboratory findings were notable for anemia (hemoglobin 9.1 g/dL), leukocytosis, elevated lactate dehydrogenase (440 U/L), a 20-pound weight loss, and prior night sweats. A comprehensive infectious workup — including blood cultures, HIV, viral hepatitis, CMV, EBV, Lyme serology, malaria PCR, and Quantiferon-TB Gold — was entirely negative, as was a myeloma screen. Imaging revealed scalp nodularity with punctate dermal calcifications on CT head, and CT abdomen/pelvis demonstrated a 2.0 cm exophytic pancreatic body mass, hepatomegaly, splenomegaly, and bilateral lymphadenopathy; MRI pancreas confirmed a suspected pancreatic neoplasm. Ultrasound-guided core biopsy of the left axillary lymph node established the diagnosis of high-grade B-cell lymphoma, and PET/CT was ordered for staging. This case highlights that scalp nodules and periorbital papules may serve as sentinel cutaneous manifestations of systemic DLBCL. Clinicians should maintain a broad oncologic differential when evaluating new scalp lesions accompanied by constitutional symptoms and lymphadenopathy, even when a competing infectious diagnosis appears compelling.