Abstract Background and Aims The classification of Lupus Nephritis (LN) plays a pivotal role in determining prognosis and guiding treatment, aligning with ISN/RPS recommendations. KDIGO and EULAR advocate for immunosuppression in cases of proliferative LN (Class III/IV) and Class V with nephrotic syndrome, while “non-proliferative” instances (Class I and II) are advised conservative care. In a contrasting approach, GLOSEN recommends immunosuppression for Class II if persistent proteinuria exceeds 1g. ISN/RPS suggests incorporating activity and chronicity indexes to further refine the classification of LN. Concerns surrounding immunosuppression in LN Class II arise from its favorable long-term kidney survival and potential drug toxicity. However, the need for caution is underscored by a 30–50% class transformation rate. Limited research comparing the long-term prognosis of treated and untreated patients exists due to the gradual progression of the disease. The use of Activity (NIH-A) and Chronicity (NIH-C) indexes, particularly in the context of protocol biopsies, offers an opportunity to reassess the perceived benign nature of LN Class II. Method In this single-center investigation, patients diagnosed with LN belonging to Class II or II+V from 1999 to 2021 were examined. Biopsies were classified according to ISN/RPS criteria and evaluated using the NIH-A and NIH-C Indexes. Patients previously diagnosed with Class III/IV LN and those experiencing class transformation to a proliferative class were excluded. We present the findings in a descriptive manner. Results Sixteen patients, with a median age of 38.5 (12 female), were included. Histological findings from the initial biopsies revealed a NIH-A of 0, with NIH-C exceeding 0 in 31% (5/16) cases. Six patients exhibited Class II plus V, with varying NIH-C scores. The primary contributors to NIH-C in the initial biopsies were tubular atrophy and interstitial fibrosis. Ten patients underwent a second biopsy after an average time lapse of 39 months (7-101). The decision for most second biopsies was based on clinical judgment rather than a standardized protocol. One patient initially diagnosed with Class II+V displayed Class II on the second biopsy, and vice versa. In 70% of patients the NIH-C increased, primarily driven by glomerulosclerosis. The rise in NIH-C scores was observed in 3/6 patients with Class II+V and in all 4 patients with isolated Class II. Most patients received mycophenolate, and 3 were treated with low-dose prednisolone. The clinical and histologic characteristics of the 10 patients who underwent a second biopsy are outlined in Tables 1 and 2. Conclusion Our limited, biased study raises questions rather than providing definitive evidence. The consistent NIH-C rise challenges Class II LN perceived benign nature. It is plausible that not all LN Class II cases are equivalent and histological variances, such as mesangial proliferation, or its focal or diffuse distribution impact outcomes. Histological variations and treatment impact on LN Class II warrant further investigation.