The grading system for the Nodular Sclerosis (NS) histotype of classical Hodgkin Lymphoma (HL) was initially proposed by the British National Lymphoma Investigation (BNLI) in 1989. Since then, the therapeutic landscape for HL has been shaken by the introduction of a PET-guided approach, as well as by that of novel agents. In this new setting, the impact carried by the two NS grades has been rarely explored. We therefore sought to evaluate how the two different NS grades affected the outcomes of HL patients treated within the modern era. Eighty-five patients treated at the University Hospital of Padova between 2016 and 2023 were enrolled. NS was graded according to the BNLI criteria, with syncytial and fibrohistiocytic variants being considered as G2. All subjects were treated with PET-adapted ABVD, with a Deauville Score >3 identifying a positive interim PET scan (PET2). Median age at diagnosis was 33 years (range 17-77), 54% of the individuals were female, 39% presented with B symptoms and 16% had bulky disease. Stage III and IV HL were both diagnosed in 20% of patients, whereas 42% had G1 NSHL and 32% had G2 NSHL. After a median follow-up of 40 months, 22% patients experienced disease relapse, with a 3-yr PFS of 76% (65-84) and no deaths being reported. The G1NS group had a significantly lower rate of PET2 positivity when compared to the other subjects (6% vs 22%; p=0.04), with the same trend being observed when the comparison was restricted only to the two NS grades (5% vs 22%; p=0.06). A significant difference in survival between the two NS grades was documented, with a 3-yr PFS of 84% for G1NS and 39% for G2NS (HR 5.7 [1.9-17.5]). Such difference was more pronounced in early-stage subjects, where no relapses were documented in G1NS patients, whereas the G2NS subgroup had a 3-yr PFS of 64% (p<0.01). Of note, the grading’s impact on PFS remained significant after adjusting for PET2 positivity in multivariate analysis (HR 4.29 [1.15-16.07]). Moreover, a drop in 3-yr PFS was seen going from G1NS PET2- (93%) to G2NS PET2- (69%) and to G2NS PET+ (33%) subjects. In summary, this study points out the value of NS grading in the contemporary era. While suffering from a low sample size, it shows how G1NS is associated with higher rates of early response, thus harbouring a remarkably good prognosis. Such information should be taken into account in the design of future studies, with the aim to tailor therapeutic strategies to the individual patient’s risk.