Background Image-guided neurosurgery, endoscopic-assisted neurosurgery and the keyhole approach are three important parts of minimally invasive neurosurgery and have played a significant role in treating skull base lesions. This study aimed to investigate the potential usefulness of coupling of the endoscope with the far lateral keyhole approach and image guidance at the ventral craniocervical junction in a cadaver model. Methods We simulated far lateral keyhole approach bilaterally in five cadaveric head specimens (10 cranial hemispheres). Computed tomography-based image guidance was used for intraoperative navigation and for quantitative measurements. Skull base structures were observed using both an operating microscope and a rigid endoscope. The jugular tubercle and one-third of the occipital condyle were then drilled, and all specimens were observed under the microscope again. We measured and compared the exposure of the petroclivus area provided by the endoscope and by the operating microscope. Statistical analysis was performed by analysis of variance followed by the Student-Newman-Keuls test. Results With endoscope assistance and image guidance, it was possible to observe the deep ventral craniocervical junction structures through three nerve gaps (among facial-acoustical nerves and the lower cranial nerves) and structures normally obstructed by the jugular tubercle and occipital condyle in the far lateral keyhole approach. The surgical area exposed in the petroclival region was significantly improved using the 0 degrees endoscope (1147.80 mm(2)) compared with the operating microscope ((756.28 +/- 50.73) mm2). The far lateral retrocondylar keyhole approach, using both 0 and 30 endoscopes, provided an exposure area ((1147.80 +/- 159.57) mm(2) and (1409.94 +/- 155.18) mm(2), respectively) greater than that of the far lateral transcondylar transtubercular keyhole approach ((1066.26 +/- 165.06) mm(2)) (P < 0.05). Conclusions With the aid of the endoscope and image guidance, it is possible to approach the ventral craniocervical junction with the far lateral keyhole approach. The use of an angled-lens endoscope can significantly improve the exposure of the petroclival region without drilling the jugular tubercle and occipital condyle.