Background Reactive lymph node hyperplasia with giant follicles (RHGF) is rare, and may occur secondary to aetiological factors of reactive follicular hyperplasia as well as following treatment of haematological malignancies. Methods/Results Case 1: A 36-year-old man with a history of chronic myeloid leukaemia in remission following tyrosine kinase inhibitor therapy presented with isolated cervical lymphadenopathy without any local and systemic symptoms. Case 2: A 52-year-old woman treated for diffuse large B-cell lymphoma 12 months previously presented with isolated cervical lymphadenopathy. She was otherwise well. In both cases, the excised lymph nodes showed florid follicular hyperplasia and paracortical expansion. The follicles were highly variable in size and shape, including several extremely large (giant) follicles. The germinal centres contained numerous tingible body macrophages, prominent apoptotic bodies and readily-identified mitotic figures, and were negative for Bcl-2. CD20 and CD79a stained many of the follicular cells, as well as moderate numbers of interfollicular cells. The cells in the inter-follicular zone consisted mainly of T cells (CD3+, CD5+ and CD7+, CD4+ > CD8+). Flow cytometry showed no evidence of monoclonality. Epstein-Barr virus was absent. Both patients remain free of their primary disease. In case 1, the lymphadenopathy resolved spontaneously after six months. Conclusions RHGF is best regarded as an extreme form of reactive follicular hyperplasia. It must be distinguished from follicular lymphoma. Careful correlation of the clinical and morphological features, immunohistochemistry, flow cytometry and cytogenetic studies is important to arrive at the correct diagnosis.