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ObjectivesCase Reporting and Surveillance (CRS) are crucial to combat the global spread of the Monkeypox virus (Mpox). To support CRS, the World Health Organization (WHO) has released standardized case definitions for suspected, probable, confirmed, and discarded cases. However, these definitions are often subject to localized adaptations by countries leading to heterogeneity in the collected data. Herein, we compared the differences in Mpox case definitions in 32 countries that collectively reported 96% of the global Mpox caseload.MethodsWe extracted information regarding Mpox case definitions issued by the competent authorities in 32 included countries for suspected, probable, confirmed, and discarded cases. All data were gathered from online public sources.ResultsFor confirmed cases, 18 countries (56%) followed WHO guidelines and tested for Mpox using species specific PCR and/or sequencing. For probable and suspected cases, seven and eight countries, respectively were found to have not released definitions in their national documentations. Furthermore, none of the countries completely matched WHO’s criteria for probable and suspected cases. Overlapping amalgamations of the criteria were frequently noticed. Regarding discarded cases, only 13 countries (41%) reported definitions, with only two countries (6%) having definition consistent with WHO guidelines. For case reporting, 12 countries (38%) were found to report both probable and confirmed cases, in line with WHO requirements.ConclusionThe heterogeneity in case definitions and reporting highlights the pressing need for homogenization in implementation of these guidelines. Homogenization would drastically improve data quality and aid data-scientists, epidemiologists, and clinicians to better understand and model the true disease burden in the society, followed by formulation and implementation of targeted interventions to curb the virus spread.