Objective: Papillary craniopharyngiomas (PCPs) represent a rare histological variant of craniopharyngiomas (CPs) usually involving the hypothalamus. This study systematically analyzes the clinical-anatomical correlation between tumor topography and symptoms related to hypothalamic dysfunction in the largest series of PCPs ever gathered. Methods: From 5,346 CP reports published from 1856 to 2021, we selected 350 well-described cases of the squamous-papillary type. Clinical presentation, tumor topography, severity of hypothalamic adhesion, patient outcome and tumor recurrence were thoroughly analyzed. Results: PCPs predominantly occur in adult (96.3%), male (61.7%) patients presenting with headache (63.4%), visual alterations (56.2%) and psychiatric disturbances (50.4%). Most PCPs are solid (50%), round (50%) lesions that occupy the third ventricle (3V, 94.8%) and show low-risk severity adhesions to the hypothalamus (66.8%). Two major topographical categories can be found: strictly 3V (57.5%), growing above an intact 3V floor (3VF) and not-strictly or infundibulo-tuberal (32.9%), expanding at the infundibulum and/or tuber cinereum. The hypothalamic syndrome predominated among strictly 3V PCPs (p<0.001). Psychiatric symptoms (p<0.001) and high-risk hypothalamic attachments (p=0.031) related to unfavorable postoperative outcomes among patients treated from 2006 onwards. The not-strictly 3V topography was identified as the major predictor of high-risk hypothalamic attachments (71.2% correctly predicted), which, along with incomplete tumor removal (p=0.018), underlies the higher tumor recurrence of this topography (p=0.001). Conclusions: This systematic review evidences that PCP topography is a major determinant of hypothalamic-related symptoms, type of hypothalamic attachments and tumor recurrence rate. Accurate preoperative definition of PCP-hypothalamus relationships is essential for the judicious, safe management of these complex lesions.