Objectives. The majority of human maxillary first molars is usually described as having three roots, but different morphologies were documented in several studies and case reports. One very rare and less investigated anatomical anomaly is the occurrence of four radicular structures in the upper first molars. This communication aimed to define the prevalence of four-rooted maxillary first molars on a meta-analytical basis. The external and internal morphology of these teeth was described by the collection of published case reports. Materials and Methods. Six electronic databases were accessed to collect case reports dealing with four-rooted maxillary first molars, as well as population-based cone-beam computed tomography (CBCT) studies. Afterward, the publications were selected according to predefined inclusion/exclusion criteria and evaluated using the Joanna Briggs Institute Critical Appraisal tool. The teeth of the chosen case reports were then independently analyzed by two dental professionals according to different dental classifications. Furthermore, the population studies were meta-analyzed to calculate the global and regional prevalence of four-rooted maxillary molars. Results. Included were forty-nine population-based CBCT studies containing 26663 maxillary first molars. Upon these data, the global incidence of four-rooted maxillary molars was meta-analytically determined as 0.047% (95%-CI:0.011–0.103%). In combination with the case reports, it was pointed out that this anomaly is distributed worldwide. Furthermore, forty-eight case reports were included containing fifty-three maxillary molars with four roots. The analyzed teeth exhibited Versiani´s pulpal chamber floor Types A and B. The majority of four-rooted maxillary first molars were classified as Type I regarding Christie's configuration. But, also 7.54% of the altered teeth could not be described by this classification. 62.34% exhibited four root canals, but also variations with five, six, or seven canals were identified. Furthermore, a significant difference was found in the occurrence rate between male and female patients. Conclusion. Due to the worldwide occurrence, dental professionals should be aware of this rare anomaly to avoid treatment errors, especially during endodontic or surgical therapies.