Lung cancer is the most common cause of cancer death worldwide with 2.21 million new cases and 1.8 million cancer deaths in 2020 [
1]. Early diagnosis is a clinically important challenge to improve prognosis. The development of low-dose chest computed tomography (CT) lung screening programs has resulted in an increased incidence of small nodules suspected of early-stage lung cancer requiring sampling to confirm malignancy [
2,
3]. Percutaneous needle aspiration has been associated with a high sensitivity (up to 90%) [
4,
5] but is limited by a significant complication rate with up to 25% pneumothorax reported in the literature [
6]. Conventional fluoroscopy-guided transbronchial biopsies are associated with significantly lower pneumothorax rates but also lower diagnostic yield, in particular for early stage small peripheral nodules [
7]. In the last years, new interventional pulmonology technologies have been to obtain safe and effective tissue collection [
8,
9] by improving navigation guidance through the bronchial pathway, device flexibility to reach lesions at tight angulation relative to the airway, and real time assessment of the relationship between the sampling device and the target lesion which can be even smaller than 1 cm. To improve navigation and lesion reach, thin/ultrathin bronchoscopes [
10], preoperative CT-based virtual bronchoscopic navigation (VBN) [
11,
12] such as electromagnetic navigational bronchoscopy (ENB) [
13], bronchoscopic transparenchymal nodule access (BTPNA) [
14], transbronchial access tools (TBAT) [
15] and robotic-assisted bronchoscopy [
16‐
18] are the main advances now available. Radial probe endobronchial ultrasound (R-EBUS) is a useful tool to study a lesion, when correctly reached [
19]. ENB has significantly improved peripheral endobronchial navigation, but remains limited by consumable cost, bronchus sign dependency and preoperative CT-to body divergence resulting in a relatively low [30–73%] diagnostic yield in particular in small lesions [
20‐
22]. The use of cone beam CT (CBCT) in combination with ENB has been described to confirm proper device position within the lesion before sampling, significantly increasing diagnostic yield to [70–83%] [
23‐
25].
CBCT is an intraoperative 3D imaging technique developed in the early 2000s and adopted as standard of care in many endovascular and percutaneous procedures to improve targeting, treatment planning and assessment [
26,
27]. In modern interventional radiology and hybrid operating rooms, CBCT-based 3D advanced procedural planning is fused on fluoroscopy to augment live guidance. CBCT and augmented fluoroscopy technical and clinical benefits have been demonstrated and their use is established in interventional radiology, interventional oncology and minimally invasive vascular surgery procedures. These technologies have recently been applied also in the field of interventional pulmonology [
27‐
29], with or without VBN [
11,
23,
30‐
32], and in thoracic surgery to streamline video-assisted resections [
33].