Abstract BACKGROUND AND AIMS Association between nephrotic syndrome (NS) and cancer is well known. However, it has been barely studied and sustained. Membranous nephropathy (MN) has often been identified as a glomerular paraneoplastic disease. Reported incidence of cancer at the time of biopsy or one year follow-up of MN is 10–20%. Incidence rates in other glomerulopathies are limited. Concomitant malignancy is associated with poor renal outcome in NS since therapy for cancer is a priority and immunosuppressive therapies for NS should be restricted. There is no consensus for cancer screening in patients with NS, with or without known risk factors for cancer. Our aim is to establish the incidence of neoplasia in a cohort of patients of two tertiary hospitals in Spain who develop NS. We analyze clinical characteristics, glomerular disease, types of malignancies and risk factors for cancer in this population. METHOD All patients > 18 years old with NS at one tertiary hospital in Madrid between January 2013 and December 2019 and at one tertiary hospital in Barcelona between January 2018 and June 2020 were included. Demographical and clinical data, laboratory results, and tests performed for cancer screening were recorded. Patients who presented cancer the year before or 24 months after the diagnosis of NS were identified. We performed a logistic regression model to identify independent risk factors for cancer in this population. RESULTS A total of 114 patients presented with NS during the study periods. A total of 57% were men, and the mean age was 57.28 ± 17.3 years. A total of 60% patients presented high blood pressure and 36% type 2 DM2; 7% patients presented HIV infection and 6% hepatitis C infection. A total of 44.7% reported smoking and 13.1% of alcohol consumption. More frequent histologic diagnosis were: diabetic nephropathy (17.5%), MN (14.9%), minimal change disease (7.9%) and membranoproliferative glomerulonephritis (7.9%). Eight patients presented positivity for anti-phospholipase A2 receptor antibodies. A total of 20 patients presented cancer (17.5%): 12 patients had a malignancy diagnosed the year before the NS onset (10 patients with solid organ malignancy and 2 patients with haematological cancer) and 8 patients 24 months after NS onset (3 patients with solid organ malignancy and 5 patients with haematological cancer). In the univariate analysis, patients with cancer were older (72.35 ± 10.28 versus 53.20 ± 17.13 years old; P < .0001). There were no differences in terms of smoking, viral infections, renal function, proteinuria or type of glomerulopathy. In a multivariate analysis, age was the only risk factor for cancer in patients with NS {OR = 1.122, [95% confidence interval (95% CI) 1.050–1.1980]; P = .0007}. Patients who were diagnosed with cancer were submitted more frequently to gastroscopy (50% versus 25.5%; P = .0323), colonoscopy (60% versus 26.6%; P = .038) and mammography (30% versus 11.7%; P = .370) as screening procedures for malignancy than those without cancer diagnosis. There were no differences in other screening procedures such as chest X-ray, fecal occult blood test, CT scan or abdominal ultrasound. CONCLUSION In our cohort, 17.5% patients with NS presented also concomitant cancer. Age was the only risk factor for neoplasia in this cohort. No association between cancer and gender, type of glomerulopathy, or known risk factors for neoplasia such as alcohol, tobacco or viral infection was found. Patients who were diagnosed with cancer were more frequently submitted to specific cancer screening procedures. It is important to develop screening strategies to find occult malignancy in patients with NS since this condition compromises renal outcome and life expectancy.