BACKGROUND The clinical significance of focal segmental glomerulosclerosis (FSGS) tip variant remains unclear. With the aim to determine its clinical and histological features, and natural history, we studied our cases of patients with this glomerular lesion. METHODS This is a retrospective analysis. All native renal biopsies from patients diagnosed as FSGS, between 1998 and 2006, were revised for cases with tip variant. Glomerulosclerosis (GS), segmental lesions and interstitial fibrosis (IF) were quantified. We analysed clinical and follow-up data and compared with cases of FSGS not otherwise specified (NOS). RESULTS In 248 primary FSGS cases, 37 corresponded to tip variant (14.9%). Median age was 17 years (range 1-65); 13 (35.1%) patients were <15 years old, and 56.8% were males. All patients had nephrotic proteinuria. At diagnosis, there were no significant differences for age, renal function and proteinuria between cases with NOS and tip variant. IF, GS and percentage of glomeruli with segmental lesions were higher in NOS than GTL (P < 0.01). At follow-up (n = 25), 15 patients received steroids alone, and 10 steroids and a cytotoxic agent. At a median follow-up of 48.7 months (24.3-86.7), 7 patients (28.0%) progressed to chronic kidney disease (CKD), 4 (16.0%) developed end-stage renal disease (ESRD) and 9 (36.0%) had complete remission. In NOS patients (n = 93), 48 (51.6%) developed CKD (P = 0.04), 20 (21.5%) developed ESRD (P = 0.54%) and 13 (14.0%) had complete remission (P = 0.02). CONCLUSIONS Our work does not demonstrate a clearly favourable prognosis in a group of patients with FSGS tip variant. Although in the tip variant there are less chronic renal tissue damage and CKD, and more frequent complete remission of the nephrotic syndrome, there is an important percentage of patients who develop CKD and ESRD.