Elevated levels of serum prolactin (PRL) are common and well described in patients with chronic renal failure. We report the case of a 4-year-old girl who also presented with premature thelarche and transient galactorrhea. Neither peritoneal dialysis nor hemodialysis reduced her extremely elevated levels of PRL, which fluctuated from time to time, probably reflecting variations in lactotroph secretion rate. Bilateral nephrectomy (BN) was eventually followed by a progressive and significant rise in PRL levels, suggesting that even uremic kidneys can eliminate PRL through tubular breakdown. Kidney transplantation was responsible for a very abrupt normalization of PRL serum levels, much faster than that observed for creatinine. This confirms animal studies suggesting that elimination of PRL occurs both through glomerular filtration and tubular breakdown. We hypothesized that the seemingly precocious puberty may have resulted from a combination of growth hormone therapy, elevated PRL and a rise in estrogens through the aromatization of adrenal androgens. This case illustrates the impact of dialysis, BN and kidney transplantation on PRL, providing new knowledge on renal PRL metabolism.