Smokeless tobacco (ST), widely used in Pakistan, poses a high risk for oral cancer. Our hospital-based data illustrate that oropharyngeal cancer (9.9%) is the second leading malignancy after breast cancer (16.1%), and is significantly higher than in other Member States of the World Health Organization’s Eastern Mediterranean Region. Urdu-speaking communities had a proportionately higher rate of oropharyngeal cancer (20.4%), followed by Balochis (19.9%), Sindhis (16.8%), Punjabis (11.7%) and Pashtuns (9.6%). Association of oropharyngeal cancer with ST use was four times higher relative to no history of tobacco use after adjusting for age, ethnicity and gender. Our findings also show a predominance of this cancer among males relative to females and one-third of the reported cases occurred among individuals under 40 years. These findings have significant social impact, indicating the need for urgent intervention against the use of ST.