(1) Background: The observational retrospective study aimed to investigate the prevalence of personality disorders (PDs) and their association with psychopathological symptoms in a group of patients with cocaine addiction. (2) Methods: Ninety-five medical records of the Pathological Addictions Service of the National Health Service of Lecce (Italy) were analyzed. PDs were diagnosed using the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II) and psychopathological symptoms were investigated through the Symptom Checklist 90-Revised (SCL-90-R). (3) Results: Ninety-two out of ninety-five patients met the criteria for at least one PD (96.8%), almost 35% had two Cluster B PDs, and over 25% had three Cluster B PDs. Nine out of ninety-five people met the criteria for all Cluster B PDs. Among the Cluster B PDs, it emerged that the most frequent diagnosis was that of narcissistic-borderline-antisocial (over 20% of the total sample). The analysis highlighted that mental suffering is prevalent in those with multiple comorbid Cluster B PDs. Specifically, depression and psychoticism exceed the clinical cut-off (T score > 63) in all patient groups. At the same time, anxiety and obsessions-compulsions are complained of only by those with more than two PDs as well as the level of general distress. Furthermore, anxiety, hostility, and paranoid ideation are significantly higher in the group of patients with more than three PDs. (4) Conclusions: Further studies should better investigate the relationship between the two aspects and describe the causal effects of PDs on psychopathological symptoms or, on the contrary, the effects of the substance on mental health and the worsening of personality alterations.