Lung cancer is among the most prevalent and most aggressive types of cancer. P53 gene abnormalities are common in lung cancer. P53 protein is an intracellular protein in tumors, recognized as independent molecular marker of aggressive tumor behavior. Chromogranins are a family of proteins, which are present in the neurosecretory granules, their identification within the tumor cells correlates with the presence of secretory activity. The aim of the present study is to detect P53 protein over-expression and Chromogranin A protein immunoreactivity in different types of lung cancer and to correlate these data with the severity of the disease. 30 out of 40 suspected cases of lung cancer were diagnosed by bronchoscopic biopsies and grouped according to the histopathological type. All cases were stained immunohistochemically for P53 protein over-expression and Chromogranin A protein immunoreactivity. Such data were correlated with the clinical, radiological and bronchoscopic findings. Statistical analysis was carried on using the frequency and Spearman Rank Order Correlation. P53 protein over-expression was detected in (76%) of cases, and this positivity showed significant correlation with the severity of the clinical, radiological and bronchoscopic findings in each type. Chromogranin A protein immunoreactivity was positive in (26%) of cases, negative in squamous cell carcinoma. this positivity was correlated with some clinical, radiological and bronchoscopic findings. So, it was concluded that, P53 protein over-expression is a good predicting factor for the severity of lung cancer, Chromogranin A protein immunoreactivity is an indicative of neuroendocrine differentiation, however it is not a reliable prognostic factor and needs to be reassessed.