This comprehensive review by Fakhoury et al. explores the potential of photoacoustic imaging (PAI) in the detection and diagnosis of cutaneous melanoma (CM). PAI, an emerging noninvasive imaging technique, uses light absorption by chromophores in tissue to generate acoustic waves, which are detected by ultrasound transducers. The review categorizes PAI systems based on their axial resolution (macroscopy, mesoscopy, and microscopy), reconstruction methods (PA tomography, raster scan PAI), and wavelength usage (single or multiple). The authors highlight the clinical significance of early detection and diagnosis of CM, emphasizing the high morbidity and mortality associated with the disease. They discuss the limitations of traditional biopsy methods and the advantages of PAI, including its ability to image microvasculature, visualize tumor boundaries, detect metastases, perform virtual histology, and identify circulating tumor cells (CTCs). The review covers a range of studies, both animal and human, demonstrating the effectiveness of PAI in detecting and staging CM. Key findings include: 1. **Melanoma Detection and Depth Measurement**: PAI has shown high sensitivity and specificity in detecting CM, with some studies achieving accurate depth measurements. Human studies using LA-PAT systems have confirmed the system's capability to visualize melanoma depths and volumes, aligning well with histopathological results. 2. **Tumor Angiogenesis**: PAI has been effective in monitoring tumor angiogenesis, visualizing new blood vessels and vascular networks within tumors. Studies using RSOM and OR-PAM have demonstrated the progression of angiogenesis over time, providing insights into tumor growth and invasion. 3. **Lymph Node Metastases**: PAI can accurately identify lymph node metastases by detecting melanin signals, which are highly absorbing in the near-infrared range. Ex vivo and in vivo studies have shown that PAI can detect micrometastases and in-transit metastases, reducing false-negative rates compared to traditional methods. 4. **Metastases to the Blood: Imaging CTCs**: PAFC (photoacoustic flow cytometry) has been used to detect CTCs in the bloodstream, accurately distinguishing them from red blood cells. Studies have shown that PAFC can detect CTCs in both healthy and melanoma patients, with some studies achieving high sensitivity and specificity. The review concludes that PAI is a promising technique for assessing CM without surgical intervention. Its ability to image microvasculature, visualize tumor boundaries, detect metastases, perform fast and label-free histology, and identify CTCs could aid in early diagnosis, classification, and monitoring of CM, including determining metastatic status.This comprehensive review by Fakhoury et al. explores the potential of photoacoustic imaging (PAI) in the detection and diagnosis of cutaneous melanoma (CM). PAI, an emerging noninvasive imaging technique, uses light absorption by chromophores in tissue to generate acoustic waves, which are detected by ultrasound transducers. The review categorizes PAI systems based on their axial resolution (macroscopy, mesoscopy, and microscopy), reconstruction methods (PA tomography, raster scan PAI), and wavelength usage (single or multiple). The authors highlight the clinical significance of early detection and diagnosis of CM, emphasizing the high morbidity and mortality associated with the disease. They discuss the limitations of traditional biopsy methods and the advantages of PAI, including its ability to image microvasculature, visualize tumor boundaries, detect metastases, perform virtual histology, and identify circulating tumor cells (CTCs). The review covers a range of studies, both animal and human, demonstrating the effectiveness of PAI in detecting and staging CM. Key findings include: 1. **Melanoma Detection and Depth Measurement**: PAI has shown high sensitivity and specificity in detecting CM, with some studies achieving accurate depth measurements. Human studies using LA-PAT systems have confirmed the system's capability to visualize melanoma depths and volumes, aligning well with histopathological results. 2. **Tumor Angiogenesis**: PAI has been effective in monitoring tumor angiogenesis, visualizing new blood vessels and vascular networks within tumors. Studies using RSOM and OR-PAM have demonstrated the progression of angiogenesis over time, providing insights into tumor growth and invasion. 3. **Lymph Node Metastases**: PAI can accurately identify lymph node metastases by detecting melanin signals, which are highly absorbing in the near-infrared range. Ex vivo and in vivo studies have shown that PAI can detect micrometastases and in-transit metastases, reducing false-negative rates compared to traditional methods. 4. **Metastases to the Blood: Imaging CTCs**: PAFC (photoacoustic flow cytometry) has been used to detect CTCs in the bloodstream, accurately distinguishing them from red blood cells. Studies have shown that PAFC can detect CTCs in both healthy and melanoma patients, with some studies achieving high sensitivity and specificity. The review concludes that PAI is a promising technique for assessing CM without surgical intervention. Its ability to image microvasculature, visualize tumor boundaries, detect metastases, perform fast and label-free histology, and identify CTCs could aid in early diagnosis, classification, and monitoring of CM, including determining metastatic status.