Abstract Follicular lymphoma is one of the commoner diagnosed Non-Hodgkin Lymphomas (NHL) of adults in the North America and Europe. It is a B-cell lymphoma, composed of neoplastic centrocytes and centroblasts that express the pan-B cell antigens CD20 and CD79a and the follicle centre markers CD10 and bcl-6. Here we report the unusual case of a 65-year-old woman presenting de novo with low-grade lymphoma. On core biopsy the H&E appearance was suggestive of follicular lymphoma, however staining for CD20 was negative. The tumour cells stained positively for CD79a and PAX-5, and CD21 staining revealed nodular meshworks of follicular dendritic cells. Fluorescent In-Situ Hybridization (FISH) detected a positive 14:18 translocation, supporting a diagnosis of follicular lymphoma. This case illustrates a potential diagnostic pitfall, especially in small needle core biopsies or where a limited panel is used. We highlight the need to be aware of aberrant immunohistochemical staining patterns and the necessity of a comprehensive panel of immunohistochemistry in lymphoma diagnosis. Ancillary molecular investigations are also critical in the evaluation of such challenging lesions.