Inflammatory breast cancer is a devastating disease with an extremely high rate of morbidity and mortality. Differentiating this disease from acute mastitis may be difficult on initial diagnosis. The expeditious diagnosis and treatment of inflammatory breast cancer has important ramifications for the patient's prognosis. Unfortunately, no clear guidelines are available to help the primary care physician differentiate between acute mastitis and inflammatory breast cancer. We present our recommendations and guidelines for a diagnostic approach to this problem. Inflammatory breast cancer typically occurs in older women, while acute mastitis usually affects younger, lactating women. If a trial of antibiotics does not decrease the signs and symptoms in the inflamed breast, inflammatory breast cancer must be considered, especially in older, nonlactating women.