An increase in the incidence of cancer, in particular skin cancer, has been observed in the last few decades. Skin cancer represents a significant public health problem in Croatia and worldwide. Cutaneous squamous cell carcinoma (cSCC) is a malignant tumor arising in epidermal keratinocytes. Together with basal cell carcinoma it belongs to non-melanoma skin cancers, which are the most common cancers in humans. The lifetime risk of cSCC development in Caucasian population is nowadays estimated to about 15%, which makes it double compared to 20 years ago. The most probable causes are increased ultraviolet light (UV) exposure (exposure to artificial UV sources in suntan parlors, spending more time outdoors, changes in fashion, as well as ozone holes), and longer life expectancy. In its etiopathogenesis, important risk factors include genetic factors, fair-skin phototype, UV exposure, chronic degenerative and inflammatory conditions, chemical factors, oncogenic viruses, immunosuppression, ionizing radiation, as well as habitual risk factors. Human epidermal growth factor receptor (HER) family is involved in the control of multiple signal pathways. Their dysregulation is associated with development of many cancers such as breast carcinoma, non-small cell lung carcinoma, ovarian carcinoma, carcinoma of pancreas, head and neck carcinoma, as well as glioblastoma. The objective of our investigation was to establish if there is association of the skin phototype and UV exposure with the expression of HER receptors, Ki67 and p53 in patients with cSCC. Study group included 101 cSCC patients. Inclusion criteria were age >50, both sexes, histopathologically confirmed cSCC, no previous therapy, specimens sufficient for immunohistochemistry, and complete clinical data collected by a questionnaire. Material obtained by excisional biopsy was completely histopathologically evaluated and additional tissue slices were immunohistochemically analyzed. Statistical analysis of the sample included non-parametrical statistical methods and statistical reviews. Analysis was done using R statistical package. Statistical significance was set at p<0.05. The following skin phototypes (according to Fitzpatrick) were present in our study: 54 (53.47%) patients with phototype II and 47 (46.53%) patients with phototype III. The majority of patients (n=93; 92.08%) were exposed to increased UV radiation during lifetime. Forty (39.60%) patients had three or more sunburns during childhood. Study results showed a signifi cantly higher expression of EGFR receptors, Ki67 and protein p53 in patients with light skin phototype that had been exposed to increased UV light during lifetime or had acquired 3 or more sunburns in childhood, suggesting that UV exposure led to the induction of EGFR, Ki67 and protein p53, and consequently to development of cSCC.