Following presentation and diagnosis, microprolactinomas usually follow a benign course and rarely progress to macroprolactinomas. However, clinically significant enlargement of prolactinomas during pregnancy, presumably related to estrogen stimulation, has been reported. This report describes a patient with amenorrhea and hyperprolactinemia and a microadenoma by computed tomography scan who developed a macroprolactinoma within 10 months after being placed on estrogen therapy. We propose that exogenous estrogen administration in this patient most likely promoted growth from a microprolactinoma to a macroprolactinoma. This case emphasizes the primary role of dopaminergic agonist therapy in the management of pathological hyperprolactinemia and suggests that estrogen therapy should not be casually given to patients with known prolactinomas to avoid the possibility of promoting tumor growth. A correlate of this approach is that caution regarding estrogen therapy should also be exercised in patients with idiopathic hyperprolactinemia who might have an occult microprolactinoma which could grow following estrogen stimulation. If estrogen treatment is deemed necessary, dopaminergic agonist therapy should also be used prophylactically to prevent potential tumor growth due to estrogen. The patient should then be carefully monitored with periodic serum PRLs and for the development of clinical manifestations suggesting pituitary growth. An imaging study should be performed when there is a significant increase in serum PRL or the development of new clinical manifestations.