Per guidelines, cancers with HER2 expression with a score of 3+ was considered HER2-positive. Cancers with scores of 0 and 1+, or those with an IHC score of 2+ and a negative ISH result, have been characterized as HER2-negative. These guideline-directed binary distinctions — HER2-positive vs HER2-negative — have until now guided physicians’ treatment decisions. New research suggests that patients with HER2-2+, ISH-negative breast cancer present a clinical picture closer to that of patients with HER2-positive breast cancer.