This case report presents a novel approach for minimally invasive fully guided apicoectomy of the palatal root of a maxillary first molar using a custom-made 3D-printed template. To date, the development of diagnostic radiographic tools such as high-resolution CBCT devices, as well as of CAD planning software and CAM technologies, like 3D printing, allow for increased application in endodontics. The patient (a 38-year-old woman) suffered from pain on the right side of the face since 4 weeks and was diagnosed with chronic apical periodontitis of the palatal root of the maxillary right first molar. The root treatment of this tooth was followed up recently and the buccal roots showed no pathologic findings. A guided apicoectomy with access from the palate was chosen as elective therapy. 3D radiographic and intraoral surface datasets were imported into an implant planning software and superimposed, and minimally invasive access to the palatal root apex was planned. Subsequently, a tooth-supported drilling template was designed and created by additive manufacturing. A flapless approach was adapted using a punch-drill and the access to the root apex as well as the apical resection were performed with a trephine drill. The connective tissue punch was finally replaced and sutured. No postoperative complication was reported and a complete remission of symptoms was reported after 2 weeks. The follow-up after 21 months showed clinically stable wound conditions and radiologically a slight reossification in the area of the palatal root tip. The presented technique may lead to novel minimally invasive approaches for the preservation of infected maxillary molars.