Trephinning or Trepanation, which is also known as trephining or trepanning, refers to the surgical practice of removing a small of bone from the skull, generally to relieve pressure on the brain. Techniques of trephinning in pre-Columbian Mesoamerica were identical to techniques practiced in the eastern hemisphere.

Trephinning involves drilling a hole into a human skull using any of several techniques. If the operation is successful, the bone begins to grow back, beginning at the rims of the hole and growing toward the center of the hole. The new bone growth is shallower than the bone at the rim, enabling scientists to determine whether a person survived after the operation. Trephinning appears to have been a truly global phenomenon, found in populations around the world dating as far back as Neolithic times.

Prior to the conceptual revolutions within the social sciences during the mid-1960s through the early 1970s, physical anthropology studies of pre-Columbian Mesoamerican populations were chiefly concerned with identifying and classifying skeletal abnormalities and exotic features such as trephinning, dental mutilation, and artificial cranial deformation . The work was primarily descriptive, with attention drawn to variations over geography and time. Because the establishment of pre-Columbian timelines was as problematic as it was important to archaeologists and physical anthropologists, focus on simply the antiquity of a practice was often a primary goal of such studies.

As the goals of archaeology and physical anthropology changed, studies of pre-Columbian Mesoamerican osseous remains began to correlate deformation practices with other cultural behaviors. A study of lesions on seventy-two intentionally-modified crania from Cholula reflecting both sexes, all ages, and chronological phases spanning 700 years concluded that the lesions appeared to have been deliberately inflicted not for pain relief but for either ritual or preventive medical purposes. A study of ten low status burials from Late Classic Monte Alban concluded that the trephinning had been applied non-therapeutically, and, since multiple techniques had been used and since some people had received more than one trephinning, the trephinning had been done experimentally. Inferring the events to represent experiments on people until they died, the study interpreted that use of trephinning as an indicator of the stressful sociopolitical climate that not long thereafter resulted in the abandonment of Monte Alban as the primary regional administrative center.