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Introduction Lymphadenopathy is a common physical finding often associated with an infectious etiology. We present a case of a patient with generalized cervical and supraclavicular lymphadenopathy diagnosed with a rare malignancy. Health care providers should be aware of some uncommon historical or physical examination findings that warrant further investigation. Clinical Findings A 16-year-old female presented to the emergency department with 3 days of a fever, congestion and sore throat with swelling around the jaw. Her physical examination findings included bilateral mandibular swelling and generalized cervical lymphadenopathy with palpable supraclavicular lymph nodes. Outcomes Complete blood count showed pancytopenia with a white blood cell count of 4.4 x 10e3/uL, hemoglobin of 10.8 g/dL and platelets of 87 x 10e3/uL. CT scan of the neck with IV contrast revealed extensive cervical and mediastinal lymphadenopathy with suspicion of lymphoma. Biopsy results diagnosed a rare form of a hematologic malignancy called blastic plasmacytoid dendritic cell neoplasm. Conclusions The presence of supraclavicular lymphadenopathy should raise concern for non-infectious etiologies, such as malignant processes.