We present clinically relevant alterations identified by OncoPanel in two patients with recurrent LGSOC: a patient with a BRAF V600E mutation who derived clinical benefit from BRAF inhibitor vemurafenib, and a patient with progressive disease after durable response to hormonal therapy whose recurrent tumor harbored an ESR1 mutation associated with resistance to antiestrogen therapy. The gene discussed is ESR1; the disease is neoplasm.