Positron emission Tomography (PET) is commonly used to stage malignancies and monitor response to treatment. This report describes two patients, one with metastatic breast cancer and the other with aggressive non-Hodgkin's lymphoma (NHL) whose responses to treatment were monitored by serial computed tomography and PET scans. In both cases after completion of systemic chemotherapy, repeat PET scanning revealed residual metabolically active tissue at the base of the neck. Because of differential therapeutic response, the possibility of different pathologic lesions was raised. In each case, further investigation with an ultrasound scan and needle biopsy revealed carcinoma of the thyroid. Both patients were subsequently treated with definitive surgery. In both described cases, a second primary malignancy was found that affected further management and in the second patient altered prognosis. This report concludes that residual metabolically active tissue on PET scans after treatment is not necessarily resistant primary disease. A mixed response requires further investigation, particularly in the case of persisting solitary abnormalities in the neck.