Summary Purpose:  Around one‐third of patients undergoing temporal lobe surgery for the treatment of intractable temporal lobe epilepsy with hippocampal sclerosis (HS) fail to become seizure‐free. Identifying reliable predictors of poor surgical outcome would be helpful in management. Atypical patterns of HS may be associated with poorer outcomes. Our aim was to identify atypical HS cases from a large surgical series and to correlate pathology with clinical and outcome data. Methods:  Quantitative neuropathologic evaluation on 165 hippocampal surgical specimens and 21 control hippocampi was carried out on NeuN‐stained sections. Neuronal densities (NDs) were measured in CA4, CA3, CA2, and CA1 subfields. The severity of granule cell dispersion (GCD) was assessed. Results:  Comparison with control ND values identified the following patterns based on the severity and distribution of neuronal loss: classical HS (CHS; n = 60) and total HS (THS; n = 39). Atypical patterns were present in 30% of cases, including end‐folium sclerosis (EFS; n = 5), CA1 predominant pattern (CA1p; n = 9), and indeterminate HS (IHS, n = 35). No HS was noted in 17 cases. Poorest outcomes were noted for no‐HS, and CA1p groups with 33–44% International League Against Epilepsy (ILAE) class I at up to 2 years follow‐up compared to 69% for CHS (p < 0.05). GCD associated with HS type (p < 0.01), but not with outcome. Conclusions:  These findings support the identification and delineation of atypical patterns of HS using quantitative methods. Atypical patterns may represent distinct clinicopathologic subtypes and may have predictive value following epilepsy surgery.