To the best of our knowledge, this is the only reported case of isolated involvement by Rosai-Dorfman disease (RDD) of small, anterior cervical-midline lymph nodes, clinically presenting as a thyroid mass. Thyroid parenchymal involvement by RDD has been reported in only 3 cases in the literature. The present case shows involvement of RDD of a pretracheal and thyroid isthmic lymph node in a 38-year-old woman. The progressively enlarging, anterior neck mass was diagnosed as "lymph node" on a fine-needle aspiration biopsy specimen and subsequently interpreted to be an isthmic cyst on ultrasonography. A magnetic resonance imaging scan revealed foci of nodularity in the thyroid isthmus and pretracheal lymph node. Excisional biopsy of the 2 masses revealed typical features of sinus histiocytosis with massive lymphadenopathy in the lymph node. Review of the patient's previous fine-needle aspiration biopsy specimens also revealed the presence of similar features. Currently, the patient is well and has no other manifestation or recurrence of RDD.