Intracerebral hemorrhage (ICH) is a frequently disabling or fatal disease. The localizationof ICH often allows an etiological association. However, in atypical/lobar ICH, the cause of bleedingis less obvious. Therefore, we present prospective histopathological and radiological studies whichwere conducted within the diagnostic workup to identify causes for lobar ICH other than hypertension.From 2016 to 2018, 198 patients with spontaneous, non-traumatic ICH requiring neurosurgicalmonitoring were enrolled in an institutional prospective patient registry. Patients with deep-seatedICH and/or hemorrhagically transformed cerebral infarcts were excluded from further analysis.Data to evaluate the source of bleeding based on histopathological and/or radiological workup wereprospectively evaluated and analyzed. After applying the inclusion criteria and excluding patientswith incomplete diagnostic workup, a total of 52 consecutive patients with lobar ICH were furtheranalyzed. Macrovascular disease was detected in 14 patients with lobar ICH (27%). In 11 patients,diagnostic workup identified cerebral amyloid angiopathy-related ICH (21%). In addition, five patientswith tumor-related ICH (10%) and six patients with ICH based on infectious pathologies(11%) were identified. In four patients, the cause of bleeding remained unknown despite extensivediagnostic workup (8%). The present prospective registry study demonstrates a higher probabilityto identify a cause of bleeding other than hypertension in patients with lobar ICH. Therefore, athorough diagnostic work-up in patients with ICH is essential to accelerate treatment and furtherimprove outcome or prevent rebleeding