Background Many studies have reported that the presence of third molars (M3s) can increase the risk of pathology in neighboring second molars (M2s). However, whether the presence of M3s can effect the mortality of M2s remains unknown. The main aim of this study was to reveal the reasons for M2 loss and how the M2 loss were related to their neighboring M3s. Methods This was a retrospective cross-sectional study. A review of the medical records and radiographic imagines of patients who had their M2(s) removed was undertaken to analyze the reasons for tooth extraction and how those reasons were related to the presence of M3s situated adjacent to the removed M2s. Results Clinical material (from January to March 2019) of 800 patients met the inclusion criteria were involved into this study. M2s in 908 quadrants (i.e. 908 M2s) were removed from these enrolled patients, wherein 382 quadrants were with the absence of M3s and the other 526 quadrants were with the presence of M3s. The average age of patients whose missing M2s had or had no neighboring M3s was 52.4 ± 14.8 years and 56.7 ± 14.9 years respectively (Mann-Whitney U test, p < 0.001). When the reasons for the 908 extracted M2s were traced, it was found that 433 teeth (47.7%) were removed due to caries and sequelae, while 300 teeth (33.0%) were lost for periodontal diseases. In addition, substantial evidence confirmed that 14.4% of the M2s with adjacent M3s were removed due to diseases mainly in the distal surface which were closely related to their neighboring M3s, and it was much higher than that was identified from removed M2s without adjacent M3s (1.8%). Except for residual roots, 42.2% M3s were removed along with neighboring M2s simultaneously. Conclusions The presence of M3s, no matter impacted or erupted M3s, was associated with an earlier loss of their neighboring M2s.