This series of serologically confirmed Lyme disease is the largest reported in the UK and represents 508 patients who presented to one hospital in the South of England between 1992 and 2012. The mean rate of borreliosis throughout this period was 9·8/100 000 population, much higher than the reported national rate of 1·7/100 000. The actual rate increased each year until 2009 when it levelled off. Patients clinically presented with rash (71%), neurological symptoms (16%, of whom half had VII cranial nerve palsies), arthropathy (8%), pyrexia (5%), cardiac abnormalities (1%) or other manifestations (<1%). Twenty percent of patients had additional non-specific symptoms of fatigue, myalgia, and cognitive changes. Serological diagnosis was with a two-tiered system of ELISA and immunoblot. There was a marked seasonal presentation in the summer months and in the first and sixth decades of life. A third of patients gave a clear history of a tick bite. The median interval between tick bite and clinical symptoms was 15 days [interquartile range (IQR) 9–28 days], with a further interval of 14 days to clinical diagnosis/treatment (IQR 2–31 days). Most cases were acquired locally and only 5% abroad. Patients responded to standard antibiotic therapy and recurrence or persistence was extremely rare. A second group of patients, not included in the clinical case series, were those who believed they had Lyme disease based on a probable tick bite but were seronegative by currently available validated tests and presented with subjective symptoms. This condition is often labelled chronic Lyme disease. These patients have a different disease from Lyme disease and therefore an alternative name, chronic arthropod-borne neuropathy (CAN), and case definition for this condition is proposed. We suggest that this chronic condition needs to be distinguished from Lyme disease, as calling the chronic illness ‘Lyme disease’ causes confusion to patients and physicians. We recommend research initiatives to investigate the aetiology, diagnosis and therapy of CAN.