The diagnosis of diabetic nephropathy (DN) is almost always based on clinical grounds. The diagnosis is supported by a long history of diabetes, evidence of target organ damage and proteinuria preceding azotemia. The validity of this clinical approach is well established in insulin dependent diabetes mellitus but not in non-insulin dependent diabetes mellitus (NIDDM). It is thus important to determine which patients with NIDDM accompanied by non-diabetic renal disease (NDRD) should have a biopsy. However, factors clinically associated with NDRD in patients with NIDDM remain unclear. Therefore we reviewed clinical data, laboratory data and renal biopsies from 22 NIDDM patients who underwent renal biopsy between 1992 and 1998 in Wonju Christian Hospital. From this data, we identified important features that would discriminate between DN and NDRD. There were 8 women and 14 men. Age ranged from 33 to 68 (51.2 ± 10.7) years. The duration of diabetes at biopsy ranged from 0 to 13 (4.2 ± 4.2) years. Nephrotic syndrome was present in 13 patients. The patients with NDRD (n = 14) and DN (n = 8) had comparable 24-hour proteinuria, 24-hour albuminuria, creatinine clearance, serum creatinine, albumin, as well as incidences of neuropathy and hypertension. The significant factors that predict the NDRD included a short duration of the diabetes mellitus, the presence of dysmorphic red blood cells in urine, the absence of retinopathy and HbA1c below 9% (p < 0.05, respectively). NDRD included IgA nephropathy (n = 6), minimal change disease (n = 3), membranous nephropathy (n = 3), membranous lupus nephritis (n = 1) and acute interstitial nephritis (n = 1). Multiple logistic regression analysis revealed that the short duration of DM and the absence of retinopathy were factors significantly associated with NDRD. In summary, when there is a short duration of diabetes mellitus, or an absence of retinopathy seen in patients with NIDDM, then renal biopsy in diabetic patients aids in the detection of NDRD.