Abstract: Objective To investigate the application of high- frequency ultrasound (HFUS) and optical coherence tomography (OCT) for monitoring the progression of cutaneous melanoma (CM) in nude mice. Methods Twenty 4-week-old nude mice were randomly divided into CM group (n=16) and control group (n=4). In CM group, A375 cell suspension were injected subcutaneously on the back of the nude mice, and only culture medium was injected in the control group. The tumor growth was monitored by gross observation and with HFUS and OCT on a daily basis. The tumor formation rate, time, and size were recorded and melanoma visibility was assessed quantitatively using the contrast- to-background-noise ratio (CNR). Twentyfour days after cell implantation, the tumors were dissected for pathological examination. Results The tumor formation rate was 87.5% in CM group. OCT detected tumor formation at an earlier time than HFUS. With the growth of the tumor, HFUS detected spots or bands of strong echoes, and flattening of the upper dermis could be observed in OCT; the of HFUS and OCT were obviously enhanced over time (P<0.05). The tumor growth curve showed that OCT was more sensitive for measurement of the tumor thickness than HFUS. The length, depth and volume of the tumors measured by HFUS were significantly greater than those measured by OCT (P<0.05). Conclusion HFUS and OCT can monitor the dynamic development of cutaneous melanoma in nude mice, and their imaging performance differs in different stages of tumor development.