The Camorra mafia has been illegally dumping and burning toxic waste for decades between Naples and the province of Caserta.
Ten million tonnes have been buried there in the last 22 years, according to environmentalist group Legambiente, and the World Health Organisation says that higher congenital abnormalities and deaths from cancer are "positively correlated" to waste exposure in the area.
"The environmental disaster... has turned to a real humanitarian tragedy," the Archbishop of Naples and bishops of local dioceses wrote in an open letter to President Giorgio Napolitano on Saturday.
"Too many are paying the price for the arrogance, abuse, incivility, greed and stupidity of criminals," the letter said, adding land had been poisoned causing "tragic and irreparable damage".
Authorities say the waste comes mostly from the industrial north and is dumped by mafia gangs for a fraction of the cost of legal disposal.
In recent months protesters have taken to the streets of Naples to demand the government do more to clean up the region. Residents have banded together on social media to document the dumping and burning of waste amid growing fears over its impact on health.