The planktonic foraminiferal species Globorotalia truncatulinoides is widely used as a biostratigraphic proxy for the Quaternary in the Mediterranean region. High-resolution quantitative studies performed on sediment cores collected in the central and western Mediterranean Sea evidence a significant abundance of G. truncatulinoides during the Middle Holocene. The robust chronological frame allows us to date this bio-event to 4.8–4.4 ka Before Present (BP), very close to the base of the Meghalayan stage (4.2 ka BP). As a consequence, we propose that G. truncatulinoides can be considered a potential marker for the Middle–Late Holocene chronological subdivision. G. truncatulinoides is a deep-dwelling planktonic foraminifer and their distributional pattern in the central and western Mediterranean Sea provides a tool to monitor the onset of the regional deep vertical mixing of the water column. During the Holocene, the significant increase in the abundance of this species is in phase with the end of African Humid Period, which marks the transition from a more humid climate to the present-day semi-arid climate.