Pain is multidimensional, and, as such, the chief reason patients seek urgent healthcare services. If inadequately assessed and untreated, pain may negatively impact on the quality of life of the patient. Treating pain is an important step in regaining control over quality of life. The objective of the present study is to examine the level of knowledge and types of approach among Italian nurses who deal with pain assessment and management. The Ferrell and McCaffery's Knowledge and Attitudes Survey Regarding Pain (KASRP) was distributed to 286 nurses employed in one of the biggest specialized hospitals in Rome, Italy. The interviewed staff work at three different settings, according to the healthcare assistance they are required to provide: intensive care unit (ICU), subintensive care unit (SICU), and ordinary ward (OW). Descriptive statistics, including frequencies and means, as well as analysis of chi-square (p< .05), were used to compare differences in scores by demographic characteristics of the participants and different settings. A logistic regression model was performed to evaluate the factors that may influence the attitude to pain and the level of knowledge of care providers. Results have shown that the odds of developing positive attitudes towards pain management were 1.62 times higher (95% CI: .92 to 2.85) in nurses employed in SICUs than in those working in OWs, while the odds of possessing a satisfactory level of knowledge was 1.76 times higher (95% CI: .93 to 3.31) among nurses in ICUs than those in OWs. A “good assessment” was better for SICU (OR = 2.17,p< .05) and ICU (OR = 3.20,p< .05) nurses. Our survey has highlighted an overall limited level of knowledge in the assessment and management of pain among the nursing staff. It is therefore a priority to implement specific training to healthcare providers from different fields, who may respond differently to patients with pain. On the other hand, further investigations are required on a greater sample of Italian nurses to better understand how to overcome the most problematic barriers to achieving good pain assessment and control.