The prenatal detection of megacystis is only the first step towards identifying the etiology and deciding on suitable treatment for this condition. Here we present a report highlighting the difficulties in the prenatal diagnosis of this severe fetal anomaly.A 28-year-old healthy primigravida was referred at 24 weeks' gestation to a tertiary hospital after an ultrasound scan at 18 weeks revealed megacystis and unilateral hydronephrosis in a male fetus with normal karyotype. On referral, a further ultrasound examination revealed a large bladder with a dilated posterior urethra (the 'keyhole sign') and normal wall thickness. Based on these findings, posterior urethral valves (PUV) syndrome was first suspected. Following weekly clinical and ultrasound surveillance, a progressive and unexpected increase in the amniotic fluid index (AFI) was observed in the third trimester, with polyhydramnios and grade IV hydronephrosis (Figures 1 and 2). These findings were suggestive of the rare megacystis-microcolonintestinal hypoperistalsis syndrome (MMIHS). Correspondence to: Dr L. Machado, Serviço de Ginecologia e Obstetrícia, Centro Hospitalar de São João, EPE, Alameda Hernani Monteiro, At 32 weeks' gestation, fetal magnetic resonance imaging (MRI) showed a dilated bladder measuring 135 × 111 × 86 mm that was compressing the abdominal organs, and severe bilateral hydronephrosis (21 mm right and 18 mm left); in addition, the stomach was clearly visible, but not the intestines (Figure 3). Vesicocentesis was performed for fetal urinalysis (sodium, potassium, calcium, phosphorus, creatinine, urea, total proteins and β2-microglobulin), and amniocentesis for evaluation of digestive enzymes (including γ-glutamyl transferase, alkaline phosphatase and biliary salts); findings from these tests were consistent with MMIHS. A Cesarean section was performed at 33 weeks, after spontaneous rupture of membranes. The neonate weighed 2950 g and had Apgar scores of 8 and 8 at 1 and 5 min, respectively. During the neonatal period the diagnosis was confirmed, and vesicostomy and total parenteral nutrition were needed. At 12 months, the infant had normal physical and neurological development, but still needed parenteral nutrition and vesicostomy.