In most cases, the diagnosis of MCDK is first suspected through prenatal ultrasound. It may be difficult, however, to distinguish MCDK from congenital hydronephrosis, which is more common. In general, however, an MCDK features cysts of various sizes in a haphazard arrangement, whereas hydronephrotic kidneys contain a large central cystic region, representing the dilated renal pelvis, surrounded by smaller cystic regions, representing the dilated calices. In addition, the cysts of a MCDK generally do not appear continuous, unlike the dilated calices seen in hydronephrosis. If MCDK and hydronephrosis cannot be differentiated based on ultrasound, a postnatal renal scan may be helpful. An MCDK will show almost no radioisotope uptake, whereas a hydronephrotic kidney will exhibit some remaining function.

Once MCDK has been diagnosed, the contralateral kidney should be carefully assessed, and regular surveillance ultrasound should be performed to monitor the growth or degeneration of the MCDK.

In the past, MCDKs were often removed to prevent the development of Wilms tumor. Further research, however, has found that the risk of Wilms tumor in the MCDK is elevated but not enough to warrant routine removal (approximately 1 : 2000 compared with 1 : 8000 in a normal kidney). As a result, MCKDs are now removed only if their size interferes with the function of adjacent organs or surveillance ultrasound demonstrates changes concerning for neoplasm. In most cases, however, the MCKD undergoes spontaneous involution, and the long-term prognosis depends on the function of the contralateral kidney.