Epidemiological studies suggest ultraviolet B (UVB) component (290-320 nm) of sun light is the most prevalent etiologic factor for skin carcinogenesis--a disease accounting for more than two million new cases each year in the USA alone. Development of UVB-induced skin carcinoma is a multistep and complex process. The molecular events that occur during UVB-induced skin carcinogenesis are poorly understood largely due to the lack of an appropriate cellular model system. Therefore, to make a progress in this area, we have developed an in vitro model for UVB-induced skin cancer using immortalized human epidermal keratinocyte (HaCaT) cells through repetitive exposure to UVB radiation. We demonstrate that UVB-transformed HaCaT cells gain enhanced proliferation rate, apoptosis-resistance, and colony- and sphere-forming abilities in a progressive manner. Moreover, these cells exhibit increased aggressiveness with enhanced migration and invasive potential and mesenchymal phenotypes. Furthermore, these derived cells are able to form aggressive squamous cell carcinoma upon inoculation into the nude mice, while parental HaCaT cells remain non-tumorigenic. Together, these novel, UVB-transformed progression model cell lines can be very helpful in gaining valuable mechanistic insight into UVB-induced skin carcinogenesis, identification of novel molecular targets of diagnostic and therapeutic significance, and in vitro screening for novel preventive and therapeutic agents.