Sixty fresh, unfixed, and unstained human liver lesions, including hepatocellular carcinomas, cholangiocarcinomas, metastatic tumors, focal nodular hyperplasias, adenomas, hemangiomas, and regenerative nodules in liver cirrhosis, underwent MPM examination and routine histopathological procedure. In the surrounding normal liver tissues, MPM images showed that the radial orientation of hepatocyte cords were around the central veins and hepatocytes were seen as one-liver-cell-thick, anastomosing, sponge-like plates, which were separated from each other by the blood-filled sinusoids [Fig. 1(a)]. These same details of cellular architecture were readily correlated with H-E images [Fig. 1(b)]. In hepatocellular carcinomas, MPM images clearly illustrated that cancer cells displayed marked cellular and nuclear pleomorphism. Cancer cells, characterized by irregular size and shape, enlarged nuclei, and increased nuclear-cytoplasmic ratio, were identified by MPM images [Fig. 1(c)], which were comparable to H-E images [Fig. 1(d)]. Moreover, in hepatocellular carcinomas, MPM imaging could significantly distinguish cancer cells from normal hepatocytes based on cell metabolism via NADH and FAD redox ratio [Fig. 1(e)], which was better in revealing cell metabolism, compared to H-E imaging [Fig. 1(f)]. The NADH and FAD redox ratio between cancer cells and normal hepatocytes was , , respectively [Fig. 1(g)]. There was significant difference (). In addition, no collagen in the intercellular space was seen in MPM imaging in hepatocellular carcinomas. Besides cell morphology and cell metabolism, tissue architecture of hepatocellular carcinomas were also seen in MPM images, which were confirmed by H-E stained images. The typical tissue architecture was trabecular or sinusoidal pattern [Figs. 2(a) and 2(b)], with exaggerated liver plates which were separated by sinusoids. The second common pattern was acinar or pseudoglandular [Figs. 2(c) and 2(d)]. Gland-like structures were formed by hepatocytes. In cholangiocarcinomas, MPM showed the clearly defined glandular and tubular structures with abundant desmoplastic stromal reaction. Dense collagenous stroma separated the glandular elements [Figs. 2(e) and 2(f)]. In liver metastatic cancers such as colorectal adenocarcinoma, MPM illustrated that normal architecture were replaced by glandular structures with cancer cells displaying marked cellular and nuclear pleomorphism [Figs. 2(g) and 2(h)]. In cavernous hemangiomas which are the most common benign conditions, MPM showed that tumors were made up of large, cavernous vascular spaces, partly or completely filled with blood separated by scant connective tissues [Figs. 3(a) and 3(b)]. In regenerative nodules in liver cirrhosis, MPM illustrated that well-defined regenerative nodules were surrounded by vascular septa, which were typically rich in elastic fibers [Figs. 3(c) and 3(d)]. In focal nodular hyperplasias (FNH), MPM demonstrated the central, stellate fibrovascular zone, which was the most characteristic feature of FNH and has the historically entrenched name of “fibrous scar” or “scar-like fibrosis”. Hepatocytes surrounding the fibrovascular zone were arranged in incomplete nodules or pseudonodules and were partially surrounded by slender fibrous septa extending from the central fibrotic zone [Figs. 3(e) and 3(f)]. In liver cell adenomas, MPM revealed that liver lesions were composed of sheets and cords of cells arranged in two-and three-cell-thick liver plates [Figs. 3(g) and 3(h)] resembling well-differentiated hepatocellular carcinomas, but the delicate strands of collagen network alongside hepatocytes could be identified. In short, MPM images were comparable to H-E images. The MPM diagnostic features for liver cancer and benign diseases were summarized in Table 2.