UVB radiation from the sun is closely associated with photocarcinogeneis of the skin. Sunscreens were used to protect the skin by reducing UVB irradiance. Sunscreen use was associated with reduction of skin cancers in clinical trials. Paradoxically, sunscreen use was associated with increased sunburn episodes in the real world settings. It was shown that UVB-induced sunburn depends on fluence but not irradiance of UVB radiation. However, we previously showed that photon density plays a critical role in UVB-induced cell differentiation. We investigated the significance photon density in the context of UVB photocarcinogenesis. For hairless mice receiving equivalent dose of UVB radiation, the low irradiance (LI) UVB treated mice induced more rapid tumor development, larger tumor burden, and more epidermal mutant p53 keratinocytes as compared to their high irradiance (HI) UVB treated counterpart. Using cultured keratinocytes, we demonstrated that LI UVB allowed more keratinocytes harboring DNA damages to enter cell cycle via ERK-related signaling as compared to its HI counterpart. These results indicated that at equivalent exposure, UVB radiation at LI has higher photocarcinogenic potential as compared to its HI counterpart. Since erythema is the observed sunburn at moderate does and use of sunscreen was not found to associate with reduction of sunburn episodes, the biological significance of sunburn with or without sunscreen use is an important clinical issue that requires further investigation.